IL-17 Augments B Cell Activation in Ocular Surface Autoimmunity

J Immunol. 2016 Nov 1;197(9):3464-3470. doi: 10.4049/jimmunol.1502641. Epub 2016 Sep 21.

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.

MeSH terms

  • Animals
  • Autoimmunity*
  • B-Lymphocytes / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Disease Models, Animal
  • Dry Eye Syndromes / immunology*
  • Female
  • Immunity, Humoral
  • Immunologic Memory
  • Interleukin-17 / physiology*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Scopolamine
  • Th17 Cells / physiology*

Substances

  • Il17a protein, mouse
  • Interleukin-17
  • Scopolamine