title: IL-17 Augments B Cell Activation in Ocular Surface Autoimmunity.
abstract: Accumulating evidence shows that IL-17 is critically involved in diverse autoimmune diseases. However, its effect on the induction and progression of the humoral immune response is not fully understood. Using a preclinical model of IL-17-mediated dry eye disease, we demonstrate that upon encountering both the BCR and a secondary T cell signal, IL-17 can enhance B cell proliferation and germinal center formation in dry eye disease mice, suggesting that a stable Ag-dependent T-B cell interaction is required. Additionally, IL-17 also promotes the differentiation of B cells into isotype-switched B cells and plasma cells. Furthermore, we show that Th17 cells are more effective than Th1 cells to provide B cell help. Reduced B cell response correlates with significant reduction in clinical disease after in vivo IL-17A neutralization. In conclusion, our findings demonstrate a new role of IL-17 in promoting autoimmunity in part through directly enhancing B cell proliferation, differentiation, and plasma cell generation.
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114.
authors.forename: Brinda
authors.initials: B
authors.lastname: Subbarayal
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Chauhan
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114.
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Zazzo
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114 Reza_Dana@meei.harvard.edu.
authors.forename: Reza
authors.identifier: 0000-0002-5732-5100
authors.initials: R
authors.lastname: Dana
mesh_terms: D000818:Animals; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000276:immunology*; D005260:Female; D056724:Immunity, Humoral; D007156:Immunologic Memory; D020381:Interleukin-17 / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D012601:Scopolamine; D058504:Th17 Cells / Q000502:physiology*
chemical_list: C098680:Il17a protein, mouse; D020381:Interleukin-17; D012601:Scopolamine