GALECTIN-3 DEFICIENCY DRIVES LUPUS-LIKE AUTOIMMUNE DISEASE BY PROMOTING SPONTANEOUS GERMINAL CENTERS FORMATION THROUGH AN IFNg - DEPENDENT MECHANISM

BECCARIA, CRISTIAN GABRIEL; FIOCCA VERNENGO, FACUNDO; TOSELLO BOARI, JIMENA; AMEZCUA VESELY, MARIA CAROLINA; RAMELLO, MARIA CECILIA; GOROSITO SERRAN, MELISA; MUCCI, JUAN; CAMPETELLA , OSCAR; MONTES, CAROLINA L.; ACOSTA RODRIGUEZ E V; GRUPPI, ADRIANA

Mar del Plata

Congreso; LXIV Reunión científica anual de la Sociedad Argentina de Inmunología, en conjunto con la reunión anual de SAIC y SAFE; 2016

Sociedad Argentina de Inmunología, en conjunto con la reunión anual de SAIC y SAFE

797 (1035) GALECTIN-3 DEFICIENCY DRIVES LUPUS-LIKEAUTOIMMUNE DISEASE BY PROMOTING SPONTANEOUSGERMINAL CENTERS FORMATION THROUGH ANIFN-ã-DEPENDENT MECHANISM.Cristian Gabriel Beccaria1, Facundo Fiocca Vernengo1,Jimena Tosello Boari1, M. Carolina Amezcua Vesely1, M.Cecilia Ramello1, Melisa Gorosito Serran1, Juan Mucci2,Oscar Campetella2, Carolina Lucía Montes1, Eva VirginiaAcosta Rodriguez1, Adriana Gruppi1.1CIBICI-CONICET, Facultad de Ciencias Químicas, UniversidadNacional de Córdoba, Córdoba, Argentina. 2Institutode Investigaciones Biotecnológicas, Universidad Nacionalde San Martín, San Martín, Argentina.Autoimmune diseases are a major health problem, affecting~10% of the developed world?s population. Since there is no curefor autoimmunity it is extremely important to study the mechanismsthat trigger these diseases. One of the hallmarks in the antibodymediatedautoimmune diseases is the spontaneous generationof Germinal Centers (GC). We have recently identified Galectin-3(Gal-3) as a critical regulator of GC formation and autoantibodyproduction. Mice lacking Gal-3 spontaneously develop a lupus-likedisease, characterized by increased numbers of GC B cells, Tfhcells, Antibody-Secreting-Cells, hyperglobulinemia, autoantibodyproduction, and mononuclear infiltration in kidneys (p < 0.05 inall cases). In the absence of Gal-3, B and T cells exhibited anactivating phenotype that appears to be comprised to GC reaction.In Gal-3 KO mice we observed increased frequencies of CD80,CD86, CXCR4, IL-21R and CD69 positive B cells (p < 0.05 in allcases) and increased percentages of CD69 and CD44 positiveCD4+T cells (p < 0.05 for both), comparably to WT counterparts.Furthermore, we found more proliferating B cells measured byKi-67 expression in Gal-3 KO mice than in WT mice (p < 0.05).Interestingly, Gal-3 KO mice produced excessive quantities ofIFN-γ, a major cytokine that has long been associated with lupusdevelopment. We observed that not only T cells could produceIFN-γ but also B cells, and these B cells expressed high levelsof IFN-ãR and T-bet. IFN-γ blockade reduced GC B cells and Tfhcell frequencies (p < 0.05 for both), and immunoglobulin classswitching, demonstrating that IFN-γ overproduction was requiredto sustain lupus-like disease. These studies demonstrate thatabsence of Gal-3 profoundly alter the immune homeostasis andsuggest that Gal-3/IFN-γ axis is a novel potential pathway fortherapeutic strategies in autoimmune diseases.