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2. Single cell profiling of circulating autoreactive CD4 T cells from patients with autoimmune liver diseases suggests tissue imprinting.

Author

Cardon, Anaïs, Guinebretière, Thomas, Dong, Chuang, Gil, Laurine, Ado, Sakina, Gavlovsky, Pierre-jean, Braud, Martin, Danger, Richard, Schultheiß, Christoph, Doméné, Aurélie, Paul-Gilloteaux, Perrine, Chevalier, Caroline, Bernier, Laura, Judor, Jean-Paul, Fourgeux, Cynthia, Imbert, Astrid, Khaldi, Marion, Bardou-Jacquet, Edouard, Elkrief, Laure, and Lannes, Adrien

Abstract

Autoimmune liver diseases (AILD) involve dysregulated CD4 T cell responses against liver self-antigens, but how these autoreactive T cells relate to liver tissue pathology remains unclear. Here we perform single-cell transcriptomic and T cell receptor analyses of circulating, self-antigen-specific CD4 T cells from patients with AILD and identify a subset of liver-autoreactive CD4 T cells with a distinct B-helper transcriptional profile characterized by PD-1, TIGIT and HLA-DR expression. These cells share clonal relationships with expanded intrahepatic T cells and exhibit transcriptional signatures overlapping with tissue-resident T cells in chronically inflamed environments. Using a mouse model, we demonstrate that, following antigen recognition in the liver, CD4 T cells acquire an exhausted phenotype, play a crucial role in liver damage, and are controlled by immune checkpoint pathways. Our findings thus suggest that circulating autoreactive CD4 T cells in AILD are imprinted by chronic antigen exposure to promote liver inflammation, thereby serving as a potential target for developing biomarkers and therapies for AILD. Dysregulated CD4 T cells have been implicated in autoimmune liver disease, but their phenotypes and origin are still unclear. Here the authors profile circulating, autoreactive CD4 T cells to find transcription signatures similar to tissue-activated, exhausted T cells, thereby hinting a tissue origin for these circulation CD4 T cells. [ABSTRACT FROM AUTHOR]

Published
2025
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3. Transcriptomic, clonal, and functional analyses reveal Liver tissue-imprinted immuno-profile of circulating autoreactive CD4 T cells in autoimmune liver diseases

Author

Cardon, Anais, primary, Guinebretiere, Thomas, additional, Dong, Chuang, additional, Gil, Laurine, additional, Ado, Sakina, additional, Gavlovsky, Pierre-jean, additional, Braud, Martin, additional, Danger, Richard, additional, Schultheiss, Christoph, additional, Domene, Aurelie, additional, Paul-Guilloteaux, Perrine, additional, Chevalier, Caroline, additional, Bernier, Laura, additional, Judor, Jean-Paul, additional, Fourgeux, Cynthia, additional, Imbert, Astrid, additional, Khaldi, Marion, additional, Bardou-Jacquet, Edouard, additional, Elkrief, Laure, additional, Lannes, Adrien, additional, Silvain, Christine, additional, Schnee, Mathieu, additional, Tanne, Florence, additional, Vavasseur, Fabienne, additional, Brusselle, Lucas, additional, Brouard, Sophie, additional, Kwok, William, additional, Mosnier, Jean-Francois, additional, Lohse, Ansgar W., additional, Poschmann, Jeremie, additional, Binder, Mascha, additional, Gournay, Jerome, additional, Conchon, Sophie, additional, Milpied, Pierre, additional, and Renand, Amedee, additional

Published
2024
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4. Cannabis use as a factor of lower corpulence in hepatitis C-infected patients: results from the ANRS CO22 Hepather cohort

Author

Barré, Tangui, Carrat, Fabrice, Ramier, Clémence, Fontaine, Hélène, Di Beo, Vincent, Bureau, Morgane, Dorival, Céline, Larrey, Dominique, Delarocque-Astagneau, Elisabeth, Mathurin, Philippe, Marcellin, Fabienne, Petrov-Sanchez, Ventzislava, Cagnot, Carole, Carrieri, Patrizia, Pol, Stanislas, Protopopescu, Camelia, Alric, Laurent, Pomes, Chloe, Zoulim, Fabien, Maynard, Marianne, Bai, Roxane, Hucault, Lucie, Bailly, François, Raffi, François, Billaud, Eric, Boutoille, David, Lefebvre, Maeva, André-Garnier, Elisabeth, Cales, Paul, Hubert, Isabelle, Lannes, Adrien, Lunel, Françoise, Boursier, Jérôme, Asselah, Tarik, Boyer, Nathalie, Giuily, Nathalie, Castelnau, Corinne, Scoazec, Giovanna, Rousseaud, Emilie, Vallet-Pichard, Anaïs, Sogni, Philippe, de Ledinghen, Victor, Foucher, Juliette, Hiriart, Jean-Baptiste, M’bouyou, Jancell, Irlès-Depé, Marie, Bourlière, Marc, Ahmed, Si Nafa Si, Oules, Valérie, Tran, Albert, Anty, Rodolphe, Gelsi, Eve, Truchi, Régine, Thabut, Dominique, Hammeche, Saloua, Moussali, Joseph, Causse, Xavier, de Dieuleveult, Barbara, Ouarani, Brahim, Labarrière, Damien, Ganne, Nathalie, Grando-Lemaire, Véronique, Nahon, Pierre, Brulé, Séverine, Ulker, Betul, Guyader, Dominique, Jezequel, Caroline, Brener, Audrey, Laligant, Anne, Rabot, Aline, Renard, Isabelle, Habersetzer, François, Baumert, Thomas, Doffoel, Michel, Mutter, Catherine, Simo-Noumbissie, Pauline, Razi, Esma, Bronowicki, Jean-Pierre, Barraud, Hélène, Bensenane, Mouni, Nani, Abdelbasset, Hassani-Nani, Sarah, Bernard, Marie-Albertine, Pageaux, Georges-Philippe, Meszaros, Magda, Metivier, Sophie, Bureau, Christophe, Morales, Thibault, Peron, Jean Marie, Robic, Marie Angèle, Decaens, Thomas, Faure, Marine, Froissart, Bruno, Hilleret, Marie-Noelle, Zarski, Jean-Pierre, Riachi, Ghassan, Goria, Odile, Paris, Fatima, Montialoux, Hélène, Leroy, Vincent, Amaddeo, Giuliana, Varaut, Anne, Simoes, Mélanie, Amzal, Rachida, Chazouillières, Olivier, Andreani, Tony, Angoulevant, Bénédicte, Chevance, Azeline, Serfaty, Lawrence, Samuel, Didier, Antonini, Teresa, Coilly, Audrey, Duclos-Vallée, Jean-Charles, Tateo, Mariagrazia, Abergel, Armand, Reymond, Maud, Brigitte, Chanteranne, Benjamin, Buchard, Muti, Léon, Geist, Claire, Conroy, Guillaume, Riffault, Raphaëlle, Rosa, Isabelle, Barrault, Camille, Costes, Laurent, Hagège, Hervé, Loustaud-Ratti, Véronique, Carrier, Paul, Debette-Gratien, Maryline, Lassailly, Guillaume, Lemaitre, Elise, Canva, Valérie, Dharancy, Sébastien, Louvet, Alexandre, Minello, Anne, Latournerie, Marianne, Bardou, Marc, Mouillot, Thomas, D’alteroche, Louis, Barbereau, Didier, Nicolas, Charlotte, Elkrief, Laure, Jaillais, Anaïs, Gournay, Jérôme, Chevalier, Caroline, Archambeaud, Isabelle, Habes, Sarah, Portal, Isabelle, Gelu-Simeon, Moana, Saillard, Eric, Lafrance, Marie-Josée, Catherine, Lucie, Chau, Frederic, Goderel, Isabelle, Lusivika-Nzinga, Clovis, Bellance, Marc-Antoine, Bellet, Jonathan, Monfalet, Priscilla, Chane-Teng, Jessica, Bijaoui, Sephora, Pannetier, Grégory, Téoulé, François, Nicol, Jérôme, Sebal, Florian, Bekhti, Rafika, Boston, Anaïs, Nailler, Laura, Le Meut, Guillaume, Diallo, Alpha, Fourati, Slim, Housset, Chantal, Bruyand, Mathias, Wittkop, Linda, Zucman-Rossi, Jessica, L’hennaff, Marianne, Sizorn, Michèle, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département d'hépatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Raymond Poincaré [Garches], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des Maladies de l'Appareil Digestif et de la Nutrition [CHRU Lille], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS)

Subjects
Endocannabinoid system, Behaviors, Δ9-Tetrahydrocannabinol, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Obesity, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Chronic, Body weight, Hepatitis C, Fibrosis, Corpulence, Cannabis, Marijuana
Abstract

Background Patients with chronic hepatitis C virus (HCV) infection are at greater risk of developing metabolic disorders. Obesity is a major risk factor for these disorders, and therefore, managing body weight is crucial. Cannabis use, which is common in these patients, has been associated with lower corpulence in various populations. However, this relationship has not yet been studied in persons with chronic HCV infection. Methods Using baseline data from the French ANRS CO22 Hepather cohort, we used binary logistic and multinomial logistic regression models to test for an inverse relationship between cannabis use (former/current) and (i) central obesity (i.e., large waist circumference) and (ii) overweight and obesity (i.e., elevated body mass index (BMI)) in patients from the cohort who had chronic HCV infection. We also tested for relationships between cannabis use and both waist circumference and BMI as continuous variables, using linear regression models. Results Among the 6348 participants in the study population, 55% had central obesity, 13.7% had obesity according to their BMI, and 12.4% were current cannabis users. After multivariable adjustment, current cannabis use was associated with lower risk of central obesity (adjusted odds ratio, aOR [95% confidence interval, CI]: 0.45 [0.37–0.55]), BMI-based obesity (adjusted relative risk ratio (aRRR) [95% CI]: 0.27 [0.19–0.39]), and overweight (aRRR [95% CI]: 0.47 [0.38–0.59]). This was also true for former use, but to a lesser extent. Former and current cannabis use were inversely associated with waist circumference and BMI. Conclusions We found that former and, to a greater extent, current cannabis use were consistently associated with smaller waist circumference, lower BMI, and lower risks of overweight, obesity, and central obesity in patients with chronic HCV infection. Longitudinal studies are needed to confirm these relationships and to assess the effect of cannabis use on corpulence and liver outcomes after HCV cure. Trial registration ClinicalTrials.gov identifier: NCT01953458.

Published
2022
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