Galectin-3 deficiency drives lupus-like disease by promoting spontaneous germinal centers formation via IFN-γ
Beccaria, C., Amezcua Vesely, M., Fiocca Vernengo, F., Gehrau, R., Ramello, M., Tosello Boari, M., Gorosito Serrán,M., Mucci, J., Piaggio, E., Campetella, O., Acosta Rodriguez, E., Montes, C. and Gruppi, A.
Centro de Investigaciones en Bioquimica Clinica e Inmunologia (CIBICI)-CONICET, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, X5000HUA, Cordoba, Argentina.
Instituto de Investigaciones Biotecnologicas (IIB-INTECH), Universidad Nacional de San Martin (UNSAM) - CONICET, B1650HMP, San Martin, Buenos Aires, Argentina.
INSERM U932, 75005, Paris, France.
Institut Curie, Section Recherche, 75005, Paris, France.
Centro de Investigaciones en Bioquimica Clinica e Inmunologia (CIBICI)-CONICET, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, X5000HUA, Cordoba, Argentina. agruppi@fcq.unc.edu.ar.
Germinal centers (GC) are important sites for high-affinity and long-lived antibody induction. Tight regulation of GC responses is critical for maintaining self-tolerance. Here, we show that Galectin-3 (Gal-3) is involved in GC development. Compared with WT mice, Gal-3 KO mice have more GC B cells and T follicular helper cells, increased percentages of antibody-secreting cells and higher concentrations of immunoglobulins and IFN-gamma in serum, and develop a lupus-like disease. IFN-gamma blockade in Gal-3 KO mice reduces spontaneous GC formation, class-switch recombination, autoantibody production and renal pathology, demonstrating that IFN-gamma overproduction sustains autoimmunity. The results from chimeric mice show that intrinsic Gal-3 signaling in B cells controls spontaneous GC formation. Taken together, our data provide evidence that Gal-3 acts directly on B cells to regulate GC responses via IFN-gamma and implicate the potential of Gal-3 as a therapeutic target in autoimmunity.
Nature Communications 9(1): 1628 (2018)