LSP1 deficiency increases IL-17-expressing T cells and accelerates primary Sjögren's syndrome.

Lymphocyte-specific protein-1 (LSP1) is known to negatively regulate T cell migration in autoimmune diseases. However, its role in the development of T cell-dependent Sjögren's syndrome remains unknown. In this study, we found that LSP1 expression was decreased in T cells in salivary glands (SGs) of mice with experimental Sjögren's syndrome, accompanied by enhanced infiltration of leukocytes into SGs. Moreover, Lsp1-/- mice had higher frequency of IL-17A-expressing T cells in cervical lymph nodes as well as increased severity in SGs than WT mice. Concurrently, LSP1 expression was reduced in human T cells of primary Sjögren's syndrome (pSS) patient. Particularly, pSS patients showed an increased Th17 cells, which inversely correlated with LSP1 expression. Taken together, these findings suggest that LSP1 deficiency promote Th17 cell development and exacerbation of pSS. LSP1 might be a potential therapeutic target to regulate Th17 response and to treat autoimmune diseases like pSS.