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1. BNT162b2 vaccine induces antibody release in saliva: a possible role for mucosal viral protection?

Author

Abbass Darwich, Chiara Pozzi, Giulia Fornasa, Michela Lizier, Elena Azzolini, Ilaria Spadoni, Francesco Carli, Antonio Voza, Antonio Desai, Carlo Ferrero, Luca Germagnoli, ICH COVID‐19 Task‐force, Alberto Mantovani, Maria Rescigno, Aghemo Alessio, Anfray Clement, Badalamenti Salvatore, Belgiovine Cristina, Bertocchi Alice, Bombace Sara, Brescia Paola, Calcaterra Francesca, Calvi Michela, Cancellara Assunta, Capucetti Arianna, Carenza Claudia, Carloni Sara, Carnevale Silvia, Cazzetta Valentina, Cecconi Maurizio, Ciccarelli Michele, Coianiz Nicolò, Darwich Abbass, Ana Lleo De Nalda, De Paoli Federica, Di Donato Rachele, Digifico Elisabeth, Durante Barbara, Farina Floriana Maria, Ferrari Valentina, Fornasa Giulia, Franzese Sara, Gil Gomez Antonio, Giugliano Silvia, Ana Rita Gomes, Lizier Michela, Lo Cascio Antonino, Melacarne Alessia, Mozzarelli Alessandro, My Ilaria, Oresta Bianca, Pasqualini Fabio, Pastò Anna, Pelamatti Erica, Perucchini Chiara, Pozzi Chiara, Rimoldi Valeria, Rimoldi Monica, Scarpa Alice, Selmi Carlo, Silvestri Alessandra, Sironi Marina, Spadoni Ilaria, Spano' Salvatore, Spata Gianmarco, Supino Domenico, Tentorio Paolo, Ummarino Aldo, Valentino Sonia, Voza Antonio, Zaghi Elisa, and Zanon Veronica

Subjects
BNT162b2, IgA, IgG, mucosal immunity, SARS‐CoV‐2, Medicine (General), R5-920, Genetics, QH426-470
Abstract

Abstract Vaccination against an airborne pathogen is very effective if it induces also the development of mucosal antibodies that can protect against infection. The mRNA‐based vaccine‐encoding SARS‐CoV‐2 full‐length spike protein (BNT162b2, Pfizer/BioNTech) protects also against infection despite being administered systemically. Here, we show that upon vaccination, cognate IgG molecules are also found in the saliva and are more abundant in SARS‐CoV‐2 previously exposed subjects, paralleling the development of plasma IgG. The antibodies titer declines at 3 months from vaccination. We identified a concentration of specific IgG in the plasma above which the relevant IgG can be detected in the saliva. Regarding IgA antibodies, we found only protease‐susceptible IgA1 antibodies in plasma while they were present at very low levels in the saliva over the course of vaccination of SARS‐CoV‐2‐naïve subjects. Thus, in response to BNT162b2 vaccine, plasma IgG can permeate into mucosal sites and participate in viral protection. It is not clear why IgA1 are detected in low amount, they may be proteolytically cleaved.

Published
2022
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2. A ‘Multiomic’ Approach of Saliva Metabolomics, Microbiota, and Serum Biomarkers to Assess the Need of Hospitalization in Coronavirus Disease 2019

Author

Chiara Pozzi, Riccardo Levi, Daniele Braga, Francesco Carli, Abbass Darwich, Ilaria Spadoni, Bianca Oresta, Carola Conca Dioguardi, Clelia Peano, Leonardo Ubaldi, Giovanni Angelotti, Barbara Bottazzi, Cecilia Garlanda, Antonio Desai, Antonio Voza, Elena Azzolini, Maurizio Cecconi, Alberto Mantovani, Giuseppe Penna, Riccardo Barbieri, Letterio S. Politi, Maria Rescigno, Aghemo Alessio, Anfray Clement, Badalamenti Salvatore, Belgiovine Cristina, Bertocchi Alice, Bombace Sara, Brescia Paola, Calcaterra Francesca, Calvi Michela, Cancellara Assunta, Capucetti Arianna, Carenza Claudia, Carloni Sara, Carnevale Silvia, Cazzetta Valentina, Cecconi Maurizio, Ciccarelli Michele, Coianiz Nicolò, Darwich Abbass, Lleo de Nalda Ana, De Paoli Federica, Di Donato Rachele, Digifico Elisabeth, Durante Barbara, FARINA Floriana Maria, Ferrari Valentina, Fornasa Giulia, Franzese Sara, Gil Gomez Antonio, Giugliano Silvia, Gomes Ana Rita, Lizier Michela, Lo Cascio Antonino, Melacarne Alessia, Mozzarelli Alessandro, My Ilaria, Oresta Bianca, Pasqualini Fabio, Pastò Anna, Pelamatti Erica, Perucchini Chiara, Pozzi Chiara, Rimoldi Valeria, Rimoldi Monica, Scarpa Alice, Selmi Carlo, Silvestri Alessandra, Sironi Marina, Spadoni Ilaria, Spano' Salvatore, Spata Gianmarco, Supino Domenico, Tentorio Paolo, Ummarino Aldo, Valentino Sonia, Voza Antonio, Zaghi Elisa, and Zanon Veronica

Subjects
Metabolome, Microbiota, CHI3L1, COVID-19, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background and Aims: The SARS-CoV-2 pandemic has overwhelmed the treatment capacity of the health care systems during the highest viral diffusion rate. Patients reaching the emergency department had to be either hospitalized (inpatients) or discharged (outpatients). Still, the decision was taken based on the individual assessment of the actual clinical condition, without specific biomarkers to predict future improvement or deterioration, and discharged patients often returned to the hospital for aggravation of their condition. Here, we have developed a new combined approach of omics to identify factors that could distinguish coronavirus disease 19 (COVID-19) inpatients from outpatients. Methods: Saliva and blood samples were collected over the course of two observational cohort studies. By using machine learning approaches, we compared salivary metabolome of 50 COVID-19 patients with that of 270 healthy individuals having previously been exposed or not to SARS-CoV-2. We then correlated the salivary metabolites that allowed separating COVID-19 inpatients from outpatients with serum biomarkers and salivary microbiota taxa differentially represented in the two groups of patients. Results: We identified nine salivary metabolites that allowed assessing the need of hospitalization. When combined with serum biomarkers, just two salivary metabolites (myo-inositol and 2-pyrrolidineacetic acid) and one serum protein, chitinase 3-like-1 (CHI3L1), were sufficient to separate inpatients from outpatients completely and correlated with modulated microbiota taxa. In particular, we found Corynebacterium 1 to be overrepresented in inpatients, whereas Actinomycetaceae F0332, Candidatus Saccharimonas, and Haemophilus were all underrepresented in the hospitalized population. Conclusion: This is a proof of concept that a combined omic analysis can be used to stratify patients independently from COVID-19.

Published
2022
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3. The long Pentraxin PTX3 serves as an early predictive biomarker of co-infections in COVID-19

Author

Accornero, Stefano, Aghemo, Alessio, Ali, Hussam, Angelini, Claudio, Arcari, Ivan, Arosio, Paola, Azzolini, Elena, Baccarin, Alessandra, Badalamenti, Salvatore, Baggio, Sara, Barbagallo, Michela, Barberi, Caterina, Barbic, Franca, Barbieri, Viviana, Barbone, Alessandro, Basciu, Alessio, Bocciolone, Monica, Borea, Federica, Borroni, Mario, Bresciani, Gianluigi, Brunetta, Enrico, Bulletti, Cinzia, Cadonati, Cristina, Calabro', Lorenzo, Calatroni, Marta, Calvetta Albania, Antonietta, Cannata, Francesco, Canziani, Lorenzo, Capretti Giovanni, Luigi, Carlani, Elisa, Carrone, Flaminia, Casana, Maddalena, Cecconi, Maurizio, Ceriotti, Carlo, Ciccarelli, Michele, Cimino, Matteo, Ciuffini, Leonardo, Colaizzi, Chiara, Colapietro, Francesca, Costa, Guido, Cozzi, Ottavia, Craviotto, Vincenzo, Crespi, Chiara, Crippa, Massimo, Da Rio, Leonardo, Dal Farra, Sara, D'Antonio, Federica, De Ambroggi, Guido, De Donato, Massimo, De Lucia, Francesca, De Santis, Maria, Delle Rose, Giacomo, Di Pilla, Marina, Dipaola, Franca, Dipasquale, Andrea, Dipasquale, Angelo, Droandi, Ginevra, Fazio, Roberta, Ferrante, Giuseppe, Ferrara Elisa, Chiara, Ferrari Matteo, Carlo, Ferri, Sebastian, Folci, Marco, Foresti, Sara, Franchi, Eloisa, Fraolini, Elia, Fugazza, Alessandro, Furfaro, Federica, Galimberti, Paola, Galtieri Alessia, Piera, Gavazzi, Francesca, Generali, Elena, Goletti, Benedetta, Guidelli, Giacomo, Jacobs, Flavia, Kurihara, Hayato, Lagioia, Michele, Libre', Luca, Lleo, Ana, Loiacono, Ferdinando, Lughezzani, Giovanni, Maccallini, Marta, Maiorino Alfonso, Francesco, Malesci, Alberto, Mantovani, Riccardo, Marchettini, Davide, Marinello, Arianna, Markopoulos, Nikolaos, Masetti, Chiara, Milani, Angelo, Mirani, Marco, Morelli, Paola, Motta, Francesca, Mundula, Valeria, Nigro, Mattia, Omodei, Paolo, Ormas, Monica, Pagliaro, Arianna, Paliotti, Roberta, Parigi Tommaso, Lorenzo, Pedale, Rosa, Pegoraro, Francesco, Pellegatta, Gaia, Pellegrino, Marta, Petriello, Gennaro, Piccini, Sara, Pocaterra, Daria, Poliani, Laura, Preatoni, Paoletta, Procopio, Fabio, Puggioni, Francesca, Pugliese, Luca, Racca, Francesca, Randazzo, Michele, Regazzoli Lancini, Damiano, Reggiani, Francesco, Rodolfi, Stefano, Ruongo, Lidia, Sacco, Clara, Sandri Maria, Teresa, Savi, Marzia, Scarfo', Iside, Shiffer, Dana, Sicoli, Federico, Solano, Simone, Solitano, Virginia, Stainer, Anna, Stella Matteo, Carlo, Strangio, Giuseppe, Taormina, Antonio, Testoni, Lucia, Tordato, Federica, Trabucco, Angela, Ulian, Luisa, Valentino, Rossella, Valeriano, Chiara, Vena, Walter, Verlingieri, Simona, Vespa, Edoardo, Voza, Antonio, Zanuso, Valentina, Zilli, Alessandra, Anfray, Clement, Belgiovine, Cristina, Bertocchi, Alice, Bombace, Sara, Brescia, Paola, Calcaterra, Francesca, Calvi, Michela, Cancellara, Assunta, Capucetti, Arianna, Carenza, Claudia, Carloni, Sara, Carnevale, Silvia, Cazzetta, Valentina, Coianiz, Nicolò, Darwich, Abbass, Davoudian, Sadaf, De Paoli, Federica, Di Donato, Rachele, Digifico, Elisabeth, Durante, Barbara, Farina Floriana, Maria, Ferrari, Valentina, Fornasa, Giulia, Franzese, Sara, Ghasemi, Somayehsadat, Gil Gomez, Antonio, Giugliano, Silvia, Gomes Ana, Rita, Lizier, Michela, Lo Cascio, Antonino, Melacarne, Alessia, Mozzarelli, Alessandro, My, Ilaria, Oresta, Bianca, Pasqualini, Fabio, Pastò, Anna, Pelamatti, Erica, Perucchini, Chiara, Pozzi, Chiara, Rimoldi, Valeria, Rimoldi, Monica, Scarpa, Alice, Scavello, Francesco, Silvestri, Alessandra, Sironi, Marina, Spadoni, Ilaria, Spano', Salvatore, Spata, Gianmarco, Supino, Domenico, Tentorio, Paolo, Ummarino, Aldo, Valentino, Sonia, Zaghi, Elisa, Zanon, Veronica, Mapelli, Sarah N., Nappi, Emanuele, García Martín, Ian David, Leone, Roberto, Angelotti, Giovanni, Zhong, Hang, Magrini, Elena, Stravalaci, Matteo, Protti, Alessandro, Santini, Alessandro, Costantini, Elena, Savevski, Victor, Bottazzi, Barbara, Bartoletti, Michele, Mantovani, Alberto, and Garlanda, Cecilia

Published
2024
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4. Biomimetic superabsorbent hydrogel acts as a gut protective dynamic exoskeleton improving metabolic parameters and expanding A. muciniphila

Author

Silvestri, Alessandra, Gil-Gomez, Antonio, Vitale, Milena, Braga, Daniele, Demitri, Christian, Brescia, Paola, Madaghiele, Marta, Spadoni, Ilaria, Jones, Bryan, Fornasa, Giulia, Mouries, Juliette, Carloni, Sara, Lizier, Michela, Romero-Gomez, Manuel, Penna, Giuseppe, Sannino, Alessandro, and Rescigno, Maria

Published
2023
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5. Mucosal overexpression of thymic stromal lymphopoietin and pro-inflammatory cytokines in patients with autoimmune atrophic gastritis

Author

Lenti, Marco Vincenzo, Facciotti, Federica, Miceli, Emanuela, Vanoli, Alessandro, Fornasa, Giulia, Lahner, Edith, Spadoni, Ilaria, Giuffrida, Paolo, Arpa, Giovanni, Pasini, Alessandra, Rovedatti, Laura, Caprioli, Flavio, Travelli, Cristina, Lattanzi, Georgia, Conti, Laura, Klersy, Catherine, Vecchi, Maurizio, Paulli, Marco, Annibale, Bruno, Corazza, Gino Roberto, Rescigno, Maria, and Di Sabatino, Antonio

Published
2022
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6. BNT162b2 vaccine induces antibody release in saliva: a possible role for mucosal viral protection?

Author

Darwich, Abbass, Pozzi, Chiara, Fornasa, Giulia, Lizier, Michela, Azzolini, Elena, Spadoni, Ilaria, Carli, Francesco, Voza, Antonio, Desai, Antonio, Ferrero, Carlo, Germagnoli, Luca, Mantovani, Alberto, Rescigno, Maria, Alessio, Aghemo, Clement, Anfray, Salvatore, Badalamenti, Cristina, Belgiovine, Alice, Bertocchi, Sara, Bombace, Paola, Brescia, Francesca, Calcaterra, Michela, Calvi, Assunta, Cancellara, Arianna, Capucetti, Claudia, Carenza, Sara, Carloni, Silvia, Carnevale, Valentina, Cazzetta, Maurizio, Cecconi, Michele, Ciccarelli, Nicolò, Coianiz, Abbass, Darwich, Lleo De Nalda, Ana, Federica, De Paoli, Rachele, Di Donato, Elisabeth, Digifico, Barbara, Durante, Maria, Farina Floriana, Valentina, Ferrari, Giulia, Fornasa, Sara, Franzese, Antonio, Gil Gomez, Silvia, Giugliano, Gomes, Ana Rita, Michela, Lizier, Antonino, Lo Cascio, Alessia, Melacarne, Alessandro, Mozzarelli, Ilaria, My, Bianca, Oresta, Fabio, Pasqualini, Anna, Pastò, Erica, Pelamatti, Chiara, Perucchini, Chiara, Pozzi, Valeria, Rimoldi, Monica, Rimoldi, Alice, Scarpa, Carlo, Selmi, Alessandra, Silvestri, Marina, Sironi, Ilaria, Spadoni, Salvatore, Spano', Gianmarco, Spata, Domenico, Supino, Paolo, Tentorio, Aldo, Ummarino, Sonia, Valentino, Antonio, Voza, Elisa, Zaghi, and Veronica, Zanon

Published
2022
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7. Mucosal Overexpression of Thymic Stromal Lymphopoietin and Proinflammatory Cytokines in Patients With Autoimmune Atrophic Gastritis

Author

Lenti, Marco Vincenzo, Facciotti, Federica, Miceli, Emanuela, Vanoli, Alessandro, Fornasa, Giulia, Lahner, Edith, Spadoni, Ilaria, Giuffrida, Paolo, Arpa, Giovanni, Pasini, Alessandra, Rovedatti, Laura, Caprioli, Flavio, Travelli, Cristina, Lattanzi, Georgia, Conti, Laura, Klersy, Catherine, Vecchi, Maurizio, Paulli, Marco, Annibale, Bruno, Corazza, Gino Roberto, Rescigno, Maria, and Di Sabatino, Antonio

Published
2022
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8. Endogenous murine microbiota member Faecalibaculum rodentium and its human homologue protect from intestinal tumour growth

Author

Zagato, Elena, Pozzi, Chiara, Bertocchi, Alice, Schioppa, Tiziana, Saccheri, Fabiana, Guglietta, Silvia, Fosso, Bruno, Melocchi, Laura, Nizzoli, Giulia, Troisi, Jacopo, Marzano, Marinella, Oresta, Bianca, Spadoni, Ilaria, Atarashi, Koji, Carloni, Sara, Arioli, Stefania, Fornasa, Giulia, Asnicar, Francesco, Segata, Nicola, Guglielmetti, Simone, Honda, Kenya, Pesole, Graziano, Vermi, William, Penna, Giuseppe, and Rescigno, Maria

Published
2020
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9. Macrophage CD31 Signaling in Dissecting Aortic Aneurysm

Author

Andreata, Francesco, Syvannarath, Varouna, Clement, Marc, Delbosc, Sandrine, Guedj, Kevin, Fornasa, Giulia, Khallou-Laschet, Jamila, Morvan, Marion, Even, Guillaume, Procopio, Emanuele, Gaston, Anh-Thu, Le Borgne, Marie, Deschamps, Lydia, Nicoletti, Antonino, and Caligiuri, Giuseppina

Published
2018
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11. Biomimetic superabsorbent hydrogel acts as a gut protective dynamic exoskeleton improving metabolic parameters and expanding A. muciniphila

Author

Gelesis, Junta de Andalucía, Silvestri, Alessandra, Gil-Gómez, Antonio, Vitale, Milena, Braga, Daniele, Demitri, Christian, Brescia, Paola, Madaghiele, Marta, Spadoni, Ilaria, Jones, Bryan, Fornasa, Giulia, Mouries, Juliette, Carloni, Sara, Lizier, Michela, Romero-Gómez, Manuel, Penna, Giuseppe, Sannino, Alessandro, Rescigno, Maria, Gelesis, Junta de Andalucía, Silvestri, Alessandra, Gil-Gómez, Antonio, Vitale, Milena, Braga, Daniele, Demitri, Christian, Brescia, Paola, Madaghiele, Marta, Spadoni, Ilaria, Jones, Bryan, Fornasa, Giulia, Mouries, Juliette, Carloni, Sara, Lizier, Michela, Romero-Gómez, Manuel, Penna, Giuseppe, Sannino, Alessandro, and Rescigno, Maria

Abstract

The rising prevalence of obesity and metabolic disorders worldwide highlights the urgent need to find new long-term and clinically meaningful weight-loss therapies. Here, we evaluate the therapeutic potential and the mechanism of action of a biomimetic cellulose-based oral superabsorbent hydrogel (OSH). Treatment with OSH exerts effects on intestinal tissue and gut microbiota composition, functioning like a protective dynamic exoskeleton. It protects from gut barrier permeability disruption and induces rapid and consistent changes in the gut microbiota composition, specifically fostering Akkermansia muciniphila expansion. The mechanobiological, physical, and chemical structures of the gel are required for A. muciniphila growth. OSH treatment induces weight loss and reduces fat accumulation, in both preventative and therapeutic settings. OSH usage also prevents liver steatosis, immune infiltration, and fibrosis, limiting the progression of non-alcoholic fatty liver disease. Our work shows the potential of using OSH as a non-systemic mechanobiological approach to treat metabolic syndrome and its comorbidities.

Published
2023

15. Abstract 3059: Microbiota mediated CHI3L1 expression as a novel candidate biomarker for breast cancer progression

Author

Mozzarelli, Alessandro Mauro, primary, Carloni, Sara, additional, Ferrrari, Valentina, additional, Giugliano, Silvia, additional, Tiraboschi, Luca, additional, Cascio, Antonino Lo, additional, Fornasa, Giulia, additional, Braga, Daniele, additional, Golzato, Davide, additional, Segata, Nicola, additional, Penna, Giuseppe, additional, and Rescigno, Maria, additional

Published
2022
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16. A 'Multiomic' Approach of Saliva Metabolomics, Microbiota, and Serum Biomarkers to Assess the Need of Hospitalization in Coronavirus Disease 2019

Author

Chiara Pozzi, Riccardo Levi, Daniele Braga, Francesco Carli, Abbass Darwich, Ilaria Spadoni, Bianca Oresta, Carola Conca Dioguardi, Clelia Peano, Leonardo Ubaldi, Giovanni Angelotti, Barbara Bottazzi, Cecilia Garlanda, Antonio Desai, Antonio Voza, Elena Azzolini, Maurizio Cecconi, Alberto Mantovani, Giuseppe Penna, Riccardo Barbieri, Letterio S. Politi, Maria Rescigno, Aghemo Alessio, Anfray Clement, Badalamenti Salvatore, Belgiovine Cristina, Bertocchi Alice, Bombace Sara, Brescia Paola, Calcaterra Francesca, Calvi Michela, Cancellara Assunta, Capucetti Arianna, Carenza Claudia, Carloni Sara, Carnevale Silvia, Cazzetta Valentina, Cecconi Maurizio, Ciccarelli Michele, Coianiz Nicolò, Darwich Abbass, Lleo de Nalda Ana, De Paoli Federica, Di Donato Rachele, Digifico Elisabeth, Durante Barbara, FARINA Floriana Maria, Ferrari Valentina, Fornasa Giulia, Franzese Sara, Gil Gomez Antonio, Giugliano Silvia, Gomes Ana Rita, Lizier Michela, Lo Cascio Antonino, Melacarne Alessia, Mozzarelli Alessandro, My Ilaria, Oresta Bianca, Pasqualini Fabio, Pastò Anna, Pelamatti Erica, Perucchini Chiara, Pozzi Chiara, Rimoldi Valeria, Rimoldi Monica, Scarpa Alice, Selmi Carlo, Silvestri Alessandra, Sironi Marina, Spadoni Ilaria, Spano' Salvatore, Spata Gianmarco, Supino Domenico, Tentorio Paolo, Ummarino Aldo, Valentino Sonia, Voza Antonio, Zaghi Elisa, and Zanon Veronica

Subjects
PCA, principal component analysis, SVM, support vector machine, ESI, electrospray ionization, FDR, false discovery rate, Microbiota, IgG, immunoglobulin G, COVID-19, LR, logistic regression, Original Research—Basic, CHI3L1, chitinase 3-like-1, ELISA, enzyme-linked immunosorbent assay, PTX3, pentraxin 3, CI, confidence interval, AUC, area under the curve, RFE, recursive feature elimination, Metabolome, CHI3L1, COVID-19, coronavirus disease 19, DT, decision tree
Abstract

Background and Aims The SARS-CoV-2 pandemic has overwhelmed the treatment capacity of the health care systems during the highest viral diffusion rate. Patients reaching the emergency department had to be either hospitalized (inpatients) or discharged (outpatients). Still, the decision was taken based on the individual assessment of the actual clinical condition, without specific biomarkers to predict future improvement or deterioration, and discharged patients often returned to the hospital for aggravation of their condition. Here, we have developed a new combined approach of omics to identify factors that could distinguish coronavirus disease 19 (COVID-19) inpatients from outpatients. Methods Saliva and blood samples were collected over the course of two observational cohort studies. By using machine learning approaches, we compared salivary metabolome of 50 COVID-19 patients with that of 270 healthy individuals having previously been exposed or not to SARS-CoV-2. We then correlated the salivary metabolites that allowed separating COVID-19 inpatients from outpatients with serum biomarkers and salivary microbiota taxa differentially represented in the two groups of patients. Results We identified nine salivary metabolites that allowed assessing the need of hospitalization. When combined with serum biomarkers, just two salivary metabolites (myo-inositol and 2-pyrrolidineacetic acid) and one serum protein, chitinase 3-like-1 (CHI3L1), were sufficient to separate inpatients from outpatients completely and correlated with modulated microbiota taxa. In particular, we found Corynebacterium 1 to be overrepresented in inpatients, whereas Actinomycetaceae F0332, Candidatus Saccharimonas, and Haemophilus were all underrepresented in the hospitalized population. Conclusion This is a proof of concept that a combined omic analysis can be used to stratify patients independently from COVID-19.

Published
2021

20. Abnormal thymic stromal lymphopoietin expression in the duodenal mucosa of patients with coeliac disease

Author

Biancheri, Paolo, primary, Di Sabatino, Antonio, additional, Rescigno, Maria, additional, Giuffrida, Paolo, additional, Fornasa, Giulia, additional, Tsilingiri, Katerina, additional, Pender, Sylvia L F, additional, Papadia, Cinzia, additional, Wood, Eleanor, additional, Pasini, Alessandra, additional, Ubezio, Cristina, additional, Vanoli, Alessandro, additional, Forbes, Alastair, additional, MacDonald, Thomas T, additional, and Corazza, Gino R, additional

Published
2015
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21. TCR stimulation drives cleavage and shedding of the ITIM receptor CD31

Author

Fornasa, Giulia, Groyer, Emilie, Clement, Marc, Dimitrov, Jordan, Compain, Caroline, Gaston, Anh-Thu, Varthaman, Aditi, Khallou-Laschet, Jamila, Newman, Debra, Graff-Dubois, Stéphanie, Nicoletti, Antonino, Caligiuri, Giuseppina, Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Blood Research Institute, BloodCenter of Wisconsin, Immunité et Infection, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR113-Université Pierre et Marie Curie - Paris 6 (UPMC), This work was supported in part by grants from the 'Fondation de France' (Engt 2006-005656 and 2008- 002724), the 'Fondation pour la Recherche Médicale' (DCV20070409268) and the 'Agence Nationale de la Recherche' (project 'RELATE' and project 'BROSCI'). G.F. is the recipient of a training grant from the 'Ministère affaires étrangères' (Egide N°636511F) and of the 'Groupe de Reflexion sur la Recherche Cardio-vasculaire et la Féderation Française de Cardiologie'. E.G. was the recipient of a research grant from the 'Fondation pour la Recherche Médicale' (FDT20071211595)., ANR: project 'RELATE and 'BROSCI',project 'RELATE and 'BROSCI', Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Hémostase, bio-ingénierie et remodelage cardiovasculaires ( LBPC ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Galilée, Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR113-Institut National de la Santé et de la Recherche Médicale ( INSERM ), ANR : project 'RELATE and 'BROSCI',project 'RELATE and 'BROSCI', Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and ANR-07-PHYS-0021,RELATE,Regulation des lymphocytes dans les manifestations atherothrombotiques(2007)

Subjects
MESH : Molecular Sequence Data, MESH: Immunoglobulins, MESH : Cell Membrane, MESH: Mice, Inbred BALB C, MESH : Mice, Inbred C57BL, MESH: Amino Acid Sequence, MESH: T-Lymphocyte Subsets, MESH: Mice, Knockout, MESH : Receptors, Antigen, T-Cell, MESH : Extracellular Space, MESH : Immunoglobulins, MESH: Protein Structure, Tertiary, MESH: Mice, Inbred C57BL, MESH : Mice, MESH : Cells, Cultured, MESH: Jurkat Cells, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH: Peptide Fragments, MESH: Lymphocyte Activation, MESH: Mice, MESH : Mice, Inbred BALB C, MESH : Jurkat Cells, MESH : Lymphocyte Activation, MESH: Molecular Sequence Data, MESH: Humans, MESH : Amino Acid Sequence, MESH : Peptide Fragments, MESH : Humans, MESH: Receptors, Antigen, T-Cell, MESH: Antigens, CD31, MESH : T-Lymphocyte Subsets, MESH: Extracellular Space, MESH : Antigens, CD31, cardiovascular system, MESH : Mice, Knockout, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Animals, MESH : Protein Structure, Tertiary, MESH: Cell Membrane, MESH: Cells, Cultured
Abstract

International audience; CD31 is a transmembrane molecule endowed with T cell regulatory functions owing to the presence of 2 immunotyrosine-based inhibitory motifs. For reasons not understood, CD31 is lost by a portion of circulating T lymphocytes, which appear prone to uncontrolled activation. In this study, we show that extracellular T cell CD31 comprising Ig-like domains 1 to 5 is cleaved and shed from the surface of human T cells upon activation via their TCR. The shed CD31 can be specifically detected as a soluble, truncated protein in human plasma. CD31 shedding results in the loss of its inhibitory function because the necessary cis-homo-oligomerization of the molecule, triggered by the trans-homophilic engagement of the distal Ig-like domain 1, cannot be established by CD31(shed) cells. However, we show that a juxta-membrane extracellular sequence, comprising part of the domain 6, remains expressed at the surface of CD31(shed) T cells. We also show that the immunosuppressive CD31 peptide aa 551-574 is highly homophilic and possibly acts by homo-oligomerizing with the truncated CD31 remaining after its cleavage and shedding. This peptide is able to sustain phosphorylation of the CD31 ITIM(686) and of SHP2 and to inhibit TCR-induced T cell activation. Finally, systemic administration of the peptide in BALB/c mice efficiently suppresses Ag-induced T cell-mediated immune responses in vivo. We conclude that the loss of T cell regulation caused by CD31 shedding driven by TCR stimulation can be rescued by molecular tools able to engage the truncated juxta-membrane extracellular molecule that remains exposed at the surface of CD31(shed) cells.

Published
2010

23. Upholding the T cell immune-regulatory function of CD31 inhibits the formation of T/B immunological synapses in vitro and attenuates the development of experimental autoimmune arthritis in vivo

Author

Clement, Marc, primary, Fornasa, Giulia, additional, Loyau, Stéphane, additional, Morvan, Marion, additional, Andreata, Francesco, additional, Guedj, Kevin, additional, Khallou-Laschet, Jamila, additional, Larghi, Paola, additional, Le Roux, Delphine, additional, Bismuth, Georges, additional, Chiocchia, Gilles, additional, Hivroz, Claire, additional, Newman, Debra K., additional, Nicoletti, Antonino, additional, and Caligiuri, Giuseppina, additional

Published
2015
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24. M1 macrophages act as LTβR-independent lymphoid tissue inducer cells during atherosclerosis-related lymphoid neogenesis

Author

Guedj, Kevin, primary, Khallou-Laschet, Jamila, additional, Clement, Marc, additional, Morvan, Marion, additional, Gaston, Anh-Thu, additional, Fornasa, Giulia, additional, Dai, Jianping, additional, Gervais-Taurel, Marianne, additional, Eberl, Gerard, additional, Michel, Jean-Baptiste, additional, Caligiuri, Giuseppina, additional, and Nicoletti, Antonino, additional

Published
2013
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26. Abnormal thymic stromal lymphopoietin expression in the duodenal mucosa of patients with coeliac disease.

Author

Biancheri, Paolo, Di Sabatino, Antonio, Rescigno, Maria, Giuffrida, Paolo, Fornasa, Giulia, Tsilingiri, Katerina, Pender, Sylvia L. F., Papadia, Cinzia, Wood, Eleanor, Pasini, Alessandra, Ubezio, Cristina, Vanoli, Alessandro, Forbes, Alastair, MacDonald, Thomas T., and Corazza, Gino R.

Subjects
CELIAC disease treatment, THYMIC stromal lymphopoietin, DUODENAL diseases, POLYMERASE chain reaction, IMMUNOBLOTTING, EPITHELIAL cells, THERAPEUTICS
Published
2016
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28. Control of T Cell Reactivation by Regulatory Qa-1–Restricted CD8+ T Cells

Author

Varthaman, Aditi, primary, Khallou-Laschet, Jamila, additional, Clement, Marc, additional, Fornasa, Giulia, additional, Kim, Hye-Jung, additional, Gaston, Anh-Thu, additional, Dussiot, Michael, additional, Caligiuri, Giuseppina, additional, Herbelin, André, additional, Kaveri, Srinivas, additional, Cantor, Harvey, additional, and Nicoletti, Antonino, additional

Published
2010
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29. Macrophage Plasticity in Experimental Atherosclerosis

Author

Khallou-Laschet, Jamila, primary, Varthaman, Aditi, additional, Fornasa, Giulia, additional, Compain, Caroline, additional, Gaston, Anh-Thu, additional, Clement, Marc, additional, Dussiot, Michaël, additional, Levillain, Olivier, additional, Graff-Dubois, Stéphanie, additional, Nicoletti, Antonino, additional, and Caligiuri, Giuseppina, additional

Published
2010
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30. Innate and adaptive immunity in self-reported nonceliac gluten sensitivity versus celiac disease

Author

A. Pasini, Tarcisio Not, Gino Roberto Corazza, Maria Rescigno, Costanza Alvisi, Paolo Giuffrida, Samuele Naviglio, Antonio Di Sabatino, Alessandro Vanoli, Luigina De Leo, Mara De Amici, C. Salvatore, Giulia Fornasa, Di Sabatino, Antonio, Giuffrida, Paolo, Fornasa, Giulia, Salvatore, Chiara, Vanoli, Alessandro, Naviglio, Samuele, DE LEO, Luigina, Pasini, Alessandra, De Amici, Mara, Alvisi, Costanza, Not, Tarcisio, Rescigno, Maria, and Corazza, Gino Roberto

Subjects
0301 basic medicine, Adult, Male, Chemokine, Thymic stromal lymphopoietin, Adolescent, Glutens, Tissue transglutaminase, Duodenum, medicine.medical_treatment, Adaptive Immunity, 03 medical and health sciences, Diet, Gluten-Free, Young Adult, 0302 clinical medicine, Immune system, Thymic Stromal Lymphopoietin, Medicine, Humans, Duodenal mucosa, Immunity, Mucosal, Cytokine, Aged, biology, Hepatology, business.industry, Medicine (all), Gastroenterology, Interleukin, Middle Aged, Acquired immune system, Immunity, Innate, Celiac Disease, 030104 developmental biology, Italy, Case-Control Studies, Immunology, biology.protein, Cytokines, 030211 gastroenterology & hepatology, Tumor necrosis factor alpha, Female, Self Report, business
Abstract

Background Immune mechanisms have been implicated in nonceliac gluten sensitivity (NCGS), a condition characterized by intestinal and/or extraintestinal symptoms caused by the ingestion of gluten in non-celiac/non-wheat allergic individuals. Aims We investigated innate and adaptive immunity in self-reported NCGS versus celiac disease (CD). Methods In the supernatants of ex vivo-cultured duodenal biopsies from 14 self-reported NCGS patients, 9 untreated and 10 treated CD patients, and 12 controls we detected innate cytokines – interleukin (IL)-15, tumor necrosis factor-α, IL-1β, IL-6, IL-12p70, IL-23, IL-27, IL-32α, thymic stromal lymphopoietin (TSLP), IFN-α-, adaptive cytokines – interferon (IFN)-γ, IL-17A, IL-4, IL-5, IL-10, IL-13-, chemokines – IL-8, CCL1, CCL2, CCL3, CCL4, CCL5, CXCL1, CXCL10-, granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF). Results Mucosal innate and adaptive cytokines, chemokines and growth factors did not differ between self-reported NCGS, treated CD and controls. On the contrary, IL-6, IL-15, IL-27, IFN-α, IFN-γ, IL-17A, IL-23, G-CSF, GM-CSF, IL-8, CCL1 and CCL4 were significantly higher in untreated CD than in self-reported NCGS, treated CD and controls, while TSLP was significantly lower in untreated CD than in self-reported NCGS, treated CD and controls. Conclusion In our hands, patients with self-reported NCGS showed no abnormalities of the mucosal immune response.

Published
2016

31. TCR stimulation drives cleavage and shedding of the ITIM receptor CD31.

Author

Fornasa G, Groyer E, Clement M, Dimitrov J, Compain C, Gaston AT, Varthaman A, Khallou-Laschet J, Newman DK, Graff-Dubois S, Nicoletti A, and Caligiuri G

Subjects
Amino Acid Sequence, Animals, Cell Membrane immunology, Cell Membrane metabolism, Cells, Cultured, Extracellular Space immunology, Extracellular Space metabolism, Humans, Immunoglobulins metabolism, Jurkat Cells, Lymphocyte Activation immunology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Molecular Sequence Data, Peptide Fragments chemical synthesis, Peptide Fragments genetics, Platelet Endothelial Cell Adhesion Molecule-1 biosynthesis, Platelet Endothelial Cell Adhesion Molecule-1 genetics, Protein Structure, Tertiary, Peptide Fragments metabolism, Platelet Endothelial Cell Adhesion Molecule-1 metabolism, Receptors, Antigen, T-Cell metabolism, Receptors, Antigen, T-Cell physiology, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism
Abstract

CD31 is a transmembrane molecule endowed with T cell regulatory functions owing to the presence of 2 immunotyrosine-based inhibitory motifs. For reasons not understood, CD31 is lost by a portion of circulating T lymphocytes, which appear prone to uncontrolled activation. In this study, we show that extracellular T cell CD31 comprising Ig-like domains 1 to 5 is cleaved and shed from the surface of human T cells upon activation via their TCR. The shed CD31 can be specifically detected as a soluble, truncated protein in human plasma. CD31 shedding results in the loss of its inhibitory function because the necessary cis-homo-oligomerization of the molecule, triggered by the trans-homophilic engagement of the distal Ig-like domain 1, cannot be established by CD31(shed) cells. However, we show that a juxta-membrane extracellular sequence, comprising part of the domain 6, remains expressed at the surface of CD31(shed) T cells. We also show that the immunosuppressive CD31 peptide aa 551-574 is highly homophilic and possibly acts by homo-oligomerizing with the truncated CD31 remaining after its cleavage and shedding. This peptide is able to sustain phosphorylation of the CD31 ITIM(686) and of SHP2 and to inhibit TCR-induced T cell activation. Finally, systemic administration of the peptide in BALB/c mice efficiently suppresses Ag-induced T cell-mediated immune responses in vivo. We conclude that the loss of T cell regulation caused by CD31 shedding driven by TCR stimulation can be rescued by molecular tools able to engage the truncated juxta-membrane extracellular molecule that remains exposed at the surface of CD31(shed) cells.

Published
2010
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