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8. Therapeutic role of interferon-γ in experimental autoimmune encephalomyelitis is mediated through a tolerogenic subset of splenic CD11b+ myeloid cells.

Author

Arellano, Gabriel, Acuña, Eric, Loda, Eileah, Moore, Lindsay, Tichauer, Juan E., Castillo, Cristian, Vergara, Fabian, Burgos, Paula I., Penaloza-MacMaster, Pablo, Miller, Stephen D., and Naves, Rodrigo

Subjects
MYELOID cells, T helper cells, REGULATORY T cells, ENCEPHALOMYELITIS, TRANSFORMING growth factors, MYELIN oligodendrocyte glycoprotein
Abstract

Cumulative evidence has established that Interferon (IFN)-γ has both pathogenic and protective roles in Multiple Sclerosis and the animal model, Experimental Autoimmune Encephalomyelitis (EAE). However, the underlying mechanisms to the beneficial effects of IFN-γ are not well understood. In this study, we found that IFN-γ exerts therapeutic effects on chronic, relapsing-remitting, and chronic progressive EAE models. The frequency of regulatory T (Treg) cells in spinal cords from chronic EAE mice treated with IFN-γ was significantly increased with no effect on Th1 and Th17 cells. Consistently, depletion of FOXP3-expressing cells blocked the protective effects of IFN-γ, indicating that the therapeutic effect of IFN-γ depends on the presence of Treg cells. However, IFN-γ did not trigger direct in vitro differentiation of Treg cells. In vivo administration of blocking antibodies against either interleukin (IL)-10, transforming growth factor (TGF)-β or program death (PD)-1, revealed that the protective effects of IFN-γ in EAE were also dependent on TGF-β and PD-1, but not on IL-10, suggesting that IFN-γ might have an indirect role on Treg cells acting through antigen-presenting cells. Indeed, IFN-γ treatment increased the frequency of a subset of splenic CD11b+ myeloid cells expressing TGF-β-Latency Associated Peptide (LAP) and program death ligand 1 (PD-L1) in a signal transducer and activator of transcription (STAT)-1-dependent manner. Furthermore, splenic CD11b+ cells from EAE mice preconditioned in vitro with IFN-γ and myelin oligodendrocyte glycoprotein (MOG) peptide exhibited a tolerogenic phenotype with the capability to induce conversion of naïve CD4+ T cells mediated by secretion of TGF-β. Remarkably, adoptive transfer of splenic CD11b+ cells from IFN-γ-treated EAE mice into untreated recipient mice ameliorated clinical symptoms of EAE and limited central nervous system infiltration of mononuclear cells and effector helper T cells. These results reveal a novel cellular and molecular mechanism whereby IFN-γ promotes beneficial effects in EAE by endowing splenic CD11b+ myeloid cells with tolerogenic and therapeutic activities. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Interferon-gamma ameliorates experimental autoimmune encephalomyelitis by inducing homeostatic adaptation of microglia.

Author

Tichauer, Juan E., Arellano, Gabriel, Acuña, Eric, González, Luis F., Kannaiyan, Nirmal R., Murgas, Paola, Panadero-Medianero, Concepción, Ibañez-Vega, Jorge, Burgos, Paula I., Loda, Eileah, Miller, Stephen D., Rossner, Moritz J., Gebicke-Haerter, Peter J., and Naves, Rodrigo

Subjects
INTERFERON gamma, ENCEPHALOMYELITIS, MYELOID cells, CENTRAL nervous system injuries, MICROGLIA, TRANSFORMING growth factors, MYASTHENIA gravis
Abstract

Compelling evidence has shown that interferon (IFN)-γ has dual effects in multiple sclerosis and in its animal model of experimental autoimmune encephalomyelitis (EAE), with results supporting both a pathogenic and beneficial function. However, the mechanisms whereby IFN-γ may promote neuroprotection in EAE and its effects on central nervous system (CNS)-resident cells have remained an enigma for more than 30 years. In this study, the impact of IFN-γ at the peak of EAE, its effects on CNS infiltrating myeloid cells (MC) and microglia (MG), and the underlying cellular and molecular mechanisms were investigated. IFN-γ administration resulted in disease amelioration and attenuation of neuroinflammation associated with significantly lower frequencies of CNS CD11b+ myeloid cells and less infiltration of inflammatory cells and demyelination. A significant reduction in activated MG and enhanced resting MG was determined by flow cytometry and immunohistrochemistry. Primary MC/MG cultures obtained from the spinal cord of IFN-γ-treated EAE mice that were ex vivo re-stimulated with a low dose (1 ng/ml) of IFN-γ and neuroantigen, promoted a significantly higher induction of CD4+ regulatory T (Treg) cells associated with increased transforming growth factor (TGF)-β secretion. Additionally, IFN-γ-treated primary MC/MG cultures produced significantly lower nitrite in response to LPS challenge than control MC/MG. IFN-γ-treated EAE mice had a significantly higher frequency of CX3CR1high MC/MG and expressed lower levels of program death ligand 1 (PD-L1) than PBS-treated mice. Most CX3CR1highPD-L1lowCD11b+Ly6G- cells expressed MG markers (Tmem119, Sall2, and P2ry12), indicating that they represented an enriched MG subset (CX3CR1highPD-L1low MG). Amelioration of clinical symptoms and induction of CX3CR1highPD-L1low MG by IFN-γ were dependent on STAT-1. RNA-seq analyses revealed that in vivo treatment with IFN-γ promoted the induction of homeostatic CX3CR1highPD-L1low MG, upregulating the expression of genes associated with tolerogenic and anti-inflammatory roles and down-regulating pro-inflammatory genes. These analyses highlight the master role that IFN-γ plays in regulating microglial activity and provide new insights into the cellular and molecular mechanisms involved in the therapeutic activity of IFN-γ in EAE. [ABSTRACT FROM AUTHOR]

Published
2023
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12. Identification of Recent Tuberculosis Exposure Using QuantiFERON-TB Gold Plus, a Multicenter Study

Author

Pérez-Recio, Sandra, primary, Pallarès, Natàlia, additional, Grijota-Camino, Maria D., additional, Sánchez-Montalvá, Adrián, additional, Barcia, Laura, additional, Campos-Gutiérrez, Silvia, additional, Pomar, Virginia, additional, Rabuñal-Rey, Ramón, additional, Balcells, María Elvira, additional, Gazel, Deniz, additional, Montiel, Natalia, additional, Vicente, Diego, additional, Goić-Barišić, Ivana, additional, Schön, Thomas, additional, Paues, Jakob, additional, Mareković, Ivana, additional, Cacho-Calvo, Juana, additional, Barac, Aleksandra, additional, Goletti, Delia, additional, García-Gasalla, Mercedes, additional, Barcala, José María, additional, Tórtola, María Teresa, additional, Anibarro, Luis, additional, Suárez-Toste, Isabel, additional, Moga, Esther, additional, Gude-Gonzalez, María J., additional, Naves, Rodrigo, additional, Karslıgil, Tekin, additional, Martin-Peñaranda, Tania, additional, Stevanovic, Goran, additional, Trigo, Matilde, additional, Rubio, Verónica, additional, Karaoğlan, İlkay, additional, Bayram, Nazan, additional, Alcaide, Fernando, additional, Tebé, Cristian, additional, and Santin, Miguel, additional

Published
2021
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14. Dysregulated Immune Responses in COVID-19 Patients Correlating With Disease Severity and Invasive Oxygen Requirements

Author

García-González, Paulina, primary, Tempio, Fabián, additional, Fuentes, Camila, additional, Merino, Consuelo, additional, Vargas, Leonardo, additional, Simon, Valeska, additional, Ramirez-Pereira, Mirliana, additional, Rojas, Verónica, additional, Tobar, Eduardo, additional, Landskron, Glauben, additional, Araya, Juan Pablo, additional, Navarrete, Mariela, additional, Bastias, Carla, additional, Tordecilla, Rocío, additional, Varas, Macarena A., additional, Maturana, Pablo, additional, Marcoleta, Andrés E., additional, Allende, Miguel L., additional, Naves, Rodrigo, additional, Hermoso, Marcela A., additional, Salazar-Onfray, Flavio, additional, Lopez, Mercedes, additional, Bono, María Rosa, additional, and Osorio, Fabiola, additional

Published
2021
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16. T helper type 1 and 17 cells determine efficacy of interferon-β in multiple sclerosis and experimental encephalomyelitis

Author

Axtell, Robert C., de Jong, Brigit A., Boniface, Katia, van der Voort, Laura F., Bhat, Roopa, De Sarno, Patrizia, Naves, Rodrigo, Han, May, Zhong, Franklin, Castellanos, Jim G., Mair, Robert, Christakos, Athena, Kolkowitz, Ilan, Katz, Liat, Killestein, Joep, Polman, Chris H., Malefyt, Rene de Waal, Steinman, Lawrence, and Raman, Chander

Subjects
Care and treatment, Research, Health aspects, Interleukins -- Health aspects -- Research, Interferon beta -- Health aspects -- Research, Multiple sclerosis -- Care and treatment -- Research, Encephalomyelitis -- Care and treatment -- Research
Abstract

IFN-β is widely prescribed for the treatment of RRMS. However, only about two thirds of patients with RRMS respond to treatment (1). Furthermore, IFN-β can exacerbate symptoms in some individuals [...], Interferon-β (IFN-β) is the major treatment for multiple sclerosis. However, this treatment is not always effective. Here we have found congruence in outcome between responses to IFN-β in experimental autoimmune encephalomyelitis (EAE) and relapsing-remitting multiple sclerosis (RRMS). IFN-β was effective in reducing EAE symptoms induced by T helper type 1 ([T.sub.H]1) cells but exacerbated disease induced by [T.sub.H]17 cells. Effective treatment in [T.sub.H]1-induced EAE correlated with increased interleukin-10 (IL-10) production by splenocytes. In [T.sub.H]17-induced disease, the amount of IL-10 was unaltered by treatment, although, unexpectedly, IFN-β treatment still reduced IL-17 production without benefit. Both inhibition of IL-17 and induction of IL-10 depended on IFN-γ. In the absence of IFN-γ signaling, IFN-β therapy was ineffective in EAE. In RRMS patients, IFN-β nonresponders had higher IL-17F concentrations in serum compared to responders. Nonresponders had worse disease with more steroid usage and more relapses than did responders. Hence, IFN-β is proinflammatory in [T.sub.H]17-induced EAE. Moreover, a high IL-17F concentration in the serum of people with RRMS is associated with nonresponsiveness to therapy with IFN-β.

Published
2010
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19. Mapeo y potencialidad de los senderos de la Universidad Federal de Lavras para educación ambiental y prácticas recreativas en la naturaleza

Author

Naves, Rodrigo da Silva, Borém, Rosângela Alves Tristão, Costa, Emanuelle Aparecida da, Oliveira, Gustavo de Sousa, Assis, Gleice Aparecida de, Assis, Franscinely Aparecida de, and Marques, Érica Alves

Subjects
Practices of recreation, Clasificación de senderos, Classification of trails, Environmental awareness, Sensibilização ambiental, Classificação das trilhas, Práticas de lazer, Conciencia ambiental, Prácticas de recreación
Abstract

Environmental Education has become a great ally for raising awareness of good health practices and living with the environment. The objective of this work was to map and classify the trails existing at the Federal University of Lavras, exposing their potential to society through lectures at state and municipal schools in the city. The trails were mapped by walking using a Garmin GPS device, model GPSMAP 62 sc. Subsequently, the collected data were transferred to the Base Camp program, which has the function of tracing the route of the route, and then the data was plotted to Google Earth, providing the satellite image of the entire length of the trail. Based on the mapping of trails at the Federal University of Lavras, areas with different degrees of declivity and floristic environments are distinguished and with diverse fauna, which instigates the suggestion of trails for students according to the age group. For elementary school students I and II, the Lagoas Trail is recommended, as it has a low degree of slope, easy access, intermediate distance and recreational spots by the lagoons for fishing practices. As for high school students, the Capela Trail and the Eucalyptus Trail, as they have a more diversified environment, would be the most designated, being even conducive to the practice of adventure activities in nature. The survey and classification of these areas can contribute to future research in other projects within the University. La Educación Ambiental se ha convertido en un gran aliado para concienciar sobre las buenas prácticas de salud y convivencia con el medio ambiente. El objetivo de este trabajo fue mapear y clasificar los senderos existentes en la Universidad Federal de Lavras, exponiendo su potencial a la sociedad a través de conferencias en escuelas estatales y municipales de la ciudad. Los senderos se mapearon caminando utilizando un dispositivo GPS Garmin, modelo GPSMAP 62 sc. Posteriormente, los datos recolectados fueron transferidos al programa Campo Base, que tiene la función de trazar la ruta de la ruta, y luego los datos fueron graficados a Google Earth, brindando la imagen satelital de toda la longitud del sendero. Con base en el mapeo de senderos de la Universidad Federal de Lavras, se distinguen áreas con diferentes grados de declive y ambientes florísticos y con fauna diversa, lo que instiga la sugerencia de senderos para los estudiantes según el grupo de edad. Para los alumnos de primaria I y II, se recomienda el sendero Lagoas, ya que tiene un grado bajo de pendiente, fácil acceso, distancia intermedia y lugares recreativos junto a las lagunas para prácticas de pesca. En cuanto a los estudiantes de secundaria, el Capela Trail y el Eucalyptus Trail, por tener un entorno más diversificado, serían los más designados, siendo incluso propicios para la práctica de actividades de aventura en la naturaleza. El relevamiento y clasificación de estas áreas puede contribuir a futuras investigaciones en otros proyectos dentro de la Universidad. A Educação Ambiental tem se tornado uma grande aliada para a conscientização de boas práticas de saúde e convivência com meio ambiente. Objetivou-se com a realização desse trabalho mapear e classificar as trilhas existentes na Universidade Federal de Lavras, expondo o potencial das mesmas à sociedade por meio de palestras nas escolas estaduais e municipais da cidade. As trilhas foram mapeadas por caminhamento usando um aparelho GPS Garmin, modelo GPSMAP 62 sc. Posteriormente os dados coletados foram transferidos para o programa Base Camp, que tem como função traçar a rota do percurso, e em seguida os dados foram plotados para o Google Earth, fornecendo a imagem por satélite de toda a extensão da trilha. Com base no mapeamento das trilhas da Universidade Federal de Lavras, distinguem-se áreas com diferentes graus de declividade e ambientes florísticos e com fauna diversificada, o que instiga a sugestão de trilhas para alunos (as) em função da faixa etária. Para discentes do Ensino Fundamental I e II recomenda-se a Trilha das Lagoas, por apresentar baixo grau de declividade, fácil acesso, distância intermediária e pontos recreativos à beira das lagoas para práticas de piquenique. Já para alunos (as) do Ensino Médio, a Trilha da Capela e Trilha dos Eucaliptos, por apresentarem um ambiente mais diversificado, seria a mais indicada, sendo inclusive propícia para prática de atividades de aventura na natureza. O levantamento e classificação dessas áreas podem contribuir para futuras pesquisas em outros projetos dentro da Universidade.

Published
2021

20. Identification of Recent Tuberculosis Exposure Using QuantiFERON-TB Gold Plus, a Multicenter Study

Author

Perez-Recio, Sandra, Pallares, Natalia, Grijota-Camino, Maria D., Sanchez-Montalva, Adrian, Barcia, Laura, Campos-Gutierrez, Silvia, Pomar, Virginia, Rabunal-Rey, Ramon, Balcells, Maria Elvira, Gazel, Deniz, Montiel, Natalia, Vicente, Diego, Goic-Barisic, Ivana, Schön, Thomas, Paues, Jakob, Marekovic, Ivana, Cacho-Calvo, Juana, Barac, Aleksandra, Goletti, Delia, Garcia-Gasalla, Mercedes, Maria Barcala, Jose, Teresa Tortola, Maria, Anibarro, Luis, Suarez-Toste, Isabel, Moga, Esther, Gude-Gonzalez, Maria J., Naves, Rodrigo, Karsligil, Tekin, Martin-Penaranda, Tania, Stevanovic, Goran, Trigo, Matilde, Rubio, Veronica, Karaoglan, Ilkay, Bayram, Nazan, Alcaide, Fernando, Tebe, Cristian, Santin, Miguel, Perez-Recio, Sandra, Pallares, Natalia, Grijota-Camino, Maria D., Sanchez-Montalva, Adrian, Barcia, Laura, Campos-Gutierrez, Silvia, Pomar, Virginia, Rabunal-Rey, Ramon, Balcells, Maria Elvira, Gazel, Deniz, Montiel, Natalia, Vicente, Diego, Goic-Barisic, Ivana, Schön, Thomas, Paues, Jakob, Marekovic, Ivana, Cacho-Calvo, Juana, Barac, Aleksandra, Goletti, Delia, Garcia-Gasalla, Mercedes, Maria Barcala, Jose, Teresa Tortola, Maria, Anibarro, Luis, Suarez-Toste, Isabel, Moga, Esther, Gude-Gonzalez, Maria J., Naves, Rodrigo, Karsligil, Tekin, Martin-Penaranda, Tania, Stevanovic, Goran, Trigo, Matilde, Rubio, Veronica, Karaoglan, Ilkay, Bayram, Nazan, Alcaide, Fernando, Tebe, Cristian, and Santin, Miguel

Abstract

We investigated whether the difference of antigen tube 2 (TB2) minus antigen tube 1 (TB1) (TB22TB1) of the QuantiFERON-TB gold plus test, which has been postulated as a surrogate for the CD81 T-cell response, could be useful in identifying recent tuberculosis (TB) exposure. We looked at the interferon gamma (IFN-g) responses and differences in TB2 and TB1 tubes for 686 adults with QFT-plus positive test results. These results were compared among groups with high (368 TB contacts), low (229 patients with immune-mediated inflammatory diseases [IMID]), and indeterminate (89 asylum seekers or people from abroad [ASPFA]) risks of recent TB exposure. A TB2-TB1 value.0.6 IU.ml(-1) was deemed to indicate a true difference between tubes. In the whole cohort, 13.6%, 10.9%, and 11.2% of cases had a TB2>TB1 result in the contact, IMID, and ASPFA groups, respectively (P = 0.591). The adjusted odds ratios (aORs) for an association between a TB2-TB1 result of >0.6 IU.ml(-1) and risk of recent exposure versus contacts were 0.71 (95% confidence interval [CI], 0.31 to 1.61) for the IMID group and 0.86 (95% CI, 0.49 to 1.52) for the ASPFA group. In TB contact subgroups, 11.4%, 15.4%, and 17.7% with close, frequent, and sporadic contact had a TB2>TB1 result (P = 0.362). The aORs versus the close subgroup were 1.29 (95% CI, 0.63 to 2.62) for the frequent subgroup and 1.55 (95% CI, 0.67 to 3.60) for the sporadic subgroup. A TB2-TB1 difference of.0.6 IU.ml(-1) was not associated with increased risk of recent TB exposure, which puts into question the clinical potential as a proxy marker for recently acquired TB infection. IMPORTANCE Contact tuberculosis tracing is essential to identify recently infected people, who therefore merit preventive treatment. However, there are no diagnostic tests that can determine whether the infection is a result of a recent exposure or not. It has been suggested that by using the QuantiFERON-TB gold plus, an interferon gamma (IFN-gamma) r, Funding Agencies|Department of Clinical Sciences of the University of Barcelona

Published
2021
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23. Systematic screening of adult household contacts of patients with active pulmonary tuberculosis reveals high rates of new infections during follow-up

Author

Balcells, María Elvira, Carvajal, Camila, Fernández, Paula, Ruiz-Tagle, Cinthya, Pizarro, Alejandra, García, Patricia, Peña, Carlos, Cuevas, Gerardo, and Naves, Rodrigo

Subjects
Latent Tuberculosis, Tuberculosis, Pulmonary, Contact Tracing, bacterial infections and mycoses
Abstract

Background: Contact investigation is cardinal in the control of tuberculosis (TB) since it helps to stop its transmission. In Chile, the National TB Program strategy does not include latent TB infection testing, regular chemoprophylaxis or follow-up in adults. Active TB was found in only 1.2% of contacts at country-level during 2018. Aim: To evaluate the performance of a systematic screening of adult household contacts with targeted chemoprophylaxis and prolonged active follow-up. Material and Methods: Prospective cohort of household contacts in Santiago. Two face-to-face visits (at 0 and 12 weeks) that included QuantiFERON TB-Gold plus tests (QFT), chest radiography (CXR) at 0 and 24 weeks and, periodic text messaging or phone call follow-up for up to 48 weeks were implemented. Contacts with positive QFT were referred for TB chemoprophylaxis. Results: A total of 200 contacts were enrolled, 69% were migrants. At baseline evaluation, 45% had a positive QFT result and 1.6% had co-prevalent active TB. At follow-up, 13% contacts further converted to QFT (+), and 5.1% more were diagnosed with active TB (mean follow-up time 32 weeks). Of these 10 further active TB cases, 6 (60%) had a negative QFT and all (100%) had normal CXR at baseline; while three cases occurred in QFT converters. Conclusions: In this cohort of household contacts, 6.7 % were diagnosed with active TB (more than 2/3 at follow-up) and 13% had a late QFT (+) conversion. Active and prolonged contacts' follow-up are essential to detect new infections and tackle the TB epidemic in Chile.

Published
2020

27. Estrategia de pesquisa sistemática y seguimiento prolongado revela alto número de nuevas infecciones tuberculosas en contactos adultos en la Región Metropolitana, Chile

Author

Balcells, María Elvira, primary, Carvajal, Camila, additional, Fernández, Paula, additional, Ruiz-Tagle, Cinthya, additional, Pizarro, Alejandra, additional, García, Patricia, additional, Peña, Carlos, additional, Cuevas, Gerardo, additional, and Naves, Rodrigo, additional

Published
2020
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29. Tuberculosis and impaired IL-23–dependent IFN-γ immunity in humans homozygous for a common TYK2 missense variant

Author

Boisson-Dupuis, Stéphanie, primary, Ramirez-Alejo, Noe, additional, Li, Zhi, additional, Patin, Etienne, additional, Rao, Geetha, additional, Kerner, Gaspard, additional, Lim, Che Kang, additional, Krementsov, Dimitry N., additional, Hernandez, Nicholas, additional, Ma, Cindy S., additional, Zhang, Qian, additional, Markle, Janet, additional, Martinez-Barricarte, Ruben, additional, Payne, Kathryn, additional, Fisch, Robert, additional, Deswarte, Caroline, additional, Halpern, Joshua, additional, Bouaziz, Matthieu, additional, Mulwa, Jeanette, additional, Sivanesan, Durga, additional, Lazarov, Tomi, additional, Naves, Rodrigo, additional, Garcia, Patricia, additional, Itan, Yuval, additional, Boisson, Bertrand, additional, Checchi, Alix, additional, Jabot-Hanin, Fabienne, additional, Cobat, Aurélie, additional, Guennoun, Andrea, additional, Jackson, Carolyn C., additional, Pekcan, Sevgi, additional, Caliskaner, Zafer, additional, Inostroza, Jaime, additional, Costa-Carvalho, Beatriz Tavares, additional, de Albuquerque, Jose Antonio Tavares, additional, Garcia-Ortiz, Humberto, additional, Orozco, Lorena, additional, Ozcelik, Tayfun, additional, Abid, Ahmed, additional, Rhorfi, Ismail Abderahmani, additional, Souhi, Hicham, additional, Amrani, Hicham Naji, additional, Zegmout, Adil, additional, Geissmann, Frédéric, additional, Michnick, Stephen W., additional, Muller-Fleckenstein, Ingrid, additional, Fleckenstein, Bernhard, additional, Puel, Anne, additional, Ciancanelli, Michael J., additional, Marr, Nico, additional, Abolhassani, Hassan, additional, Balcells, María Elvira, additional, Condino-Neto, Antonio, additional, Strickler, Alexis, additional, Abarca, Katia, additional, Teuscher, Cory, additional, Ochs, Hans D., additional, Reisli, Ismail, additional, Sayar, Esra H., additional, El-Baghdadi, Jamila, additional, Bustamante, Jacinta, additional, Hammarström, Lennart, additional, Tangye, Stuart G., additional, Pellegrini, Sandra, additional, Quintana-Murci, Lluis, additional, Abel, Laurent, additional, and Casanova, Jean-Laurent, additional

Published
2018
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30. Glucocorticoids Impair Phagocytosis and Inflammatory Response Against Crohn’s Disease-Associated Adherent-Invasive Escherichia coli

Author

Olivares-Morales, Mauricio Javier, primary, De La Fuente, Marjorie Katherine, additional, Dubois-Camacho, Karen, additional, Parada, Daniela, additional, Diaz-Jiménez, David, additional, Torres-Riquelme, Alejandro, additional, Xu, Xiaojiang, additional, Chamorro-Veloso, Nayaret, additional, Naves, Rodrigo, additional, Gonzalez, Maria-Julieta, additional, Quera, Rodrigo, additional, Figueroa, Carolina, additional, Cidlowski, John Anthony, additional, Vidal, Roberto Mauricio, additional, and Hermoso, Marcela Alejandra, additional

Published
2018
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32. Galectin-8 as an immunosuppressor in experimental autoimmune encephalomyelitis and a target of human early prognostic antibodies in multiple sclerosis

Author

Pardo, Evelyn, primary, Cárcamo, Claudia, additional, Uribe-San Martín, Reinaldo, additional, Ciampi, Ethel, additional, Segovia-Miranda, Fabián, additional, Curkovic-Peña, Cristobal, additional, Montecino, Fabián, additional, Holmes, Christopher, additional, Tichauer, Juan Enrique, additional, Acuña, Eric, additional, Osorio-Barrios, Francisco, additional, Castro, Marjorie, additional, Cortes, Priscilla, additional, Oyanadel, Claudia, additional, Valenzuela, David M., additional, Pacheco, Rodrigo, additional, Naves, Rodrigo, additional, Soza, Andrea, additional, and González, Alfonso, additional

Published
2017
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33. Association of vitamin D deficiency, season of the year, and latent tuberculosis infection among household contacts

Author

Balcells, María Elvira, primary, García, Patricia, additional, Tiznado, Camila, additional, Villarroel, Luis, additional, Scioscia, Natalia, additional, Carvajal, Camila, additional, Zegna-Ratá, Francesca, additional, Hernández, Mariluz, additional, Meza, Paulina, additional, González, Luis F., additional, Peña, Carlos, additional, and Naves, Rodrigo, additional

Published
2017
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35. The interdependent, overlapping and differential roles of type I and type II interferons in the pathogenesis of experimental autoimmune encephalomyelitis1

Author

Naves, Rodrigo, Singh, Simer P., Cashman, Kevin S., Rowse, Amber L., Axtell, Robert C., Steinman, Lawrence, Mountz, John D., Steele, Chad, De Sarno, Patrizia, and Raman, Chander

Subjects
Mice, Inbred C57BL, Mice, Knockout, Interferon-gamma, Mice, Encephalomyelitis, Autoimmune, Experimental, Interferon Type I, Animals, Th17 Cells, Adoptive Transfer, Immunohistochemistry, Article, Signal Transduction
Abstract

Type I IFNs (IFN-α and IFN-β) and type II IFN (IFN-γ) mediate both regulation and inflammation in multiple sclerosis (MS), neuromyelitis optica (NMO) and in experimental autoimmune encephalomyelitis (EAE). However the underlying mechanism for these Janus-like activities of type I and II IFNs in neuroinflammation remains unclear. Although endogenous type I IFN-signaling provides a protective response in neuroinflammation, we find that when IFN-γ signaling is ablated, type I IFNs drive inflammation resulting in exacerbated EAE. IFN-γ has disease stage-specific opposing function in EAE. Treatment of mice with IFN-γ during initiation phase of EAE leads to enhanced severity of disease. In contrast, IFN-γ treatment during effector phase attenuated disease. This immunosuppressive activity of IFN-γ required functional type I IFN-signaling. In IFN-α/β receptor (IFNAR) deficient mice, IFN-γ treatment during effector phase of EAE exacerbated disease. Using an adoptive transfer-EAE model, we found that T-cell intrinsic type I and type II IFN signals are simultaneously required to establish chronic EAE by encephalitogenic Th1 cells. However in Th17 cells loss of either IFN signals leads to the development of a severe chronic disease. The data implies that type I and type II IFN signals have independent but non-redundant role in restraining encephalitogenic Th17 cells in vivo. Overall our data show that type I and type II IFNs function in an integrated manner to regulate the pathogenesis in EAE.

Published
2013

43. Transgenic Expression of Soluble Human CD5 Enhances Experimentally-Induced Autoimmune and Anti-Tumoral Immune Responses

Author

Fenutría, Rafael, primary, Martinez, Vanesa G., additional, Simões, Inês, additional, Postigo, Jorge, additional, Gil, Victor, additional, Martínez-Florensa, Mario, additional, Sintes, Jordi, additional, Naves, Rodrigo, additional, Cashman, Kevin S., additional, Alberola-Ila, José, additional, Ramos-Casals, Manel, additional, Soldevila, Gloria, additional, Raman, Chander, additional, Merino, Jesús, additional, Merino, Ramón, additional, Engel, Pablo, additional, and Lozano, Francisco, additional

Published
2014
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