Faculty Opinions recommendation of Cutting edge: an NK cell-independent role for Slamf4 in controlling humoral autoimmunity.

Abstract

Several genes within a syntenic region of human and mouse chromosome 1 are associated with predisposition to systemic lupus erythematosus. Analyses of lupus-prone congenic mice have pointed to an important role for the signaling lymphocyte activation molecule family (slamf)6 surface receptor in lupus pathogenesis. In this article, we demonstrate that a second member of the Slamf gene family, Slamf4 (Cd244), contributes to lupus-related autoimmunity. B6.Slamf4(-/-) mice spontaneously develop activated CD4 T cells and B cells and increased numbers of T follicular helper cells and a proportion develop autoantibodies to nuclear Ags. B6.Slamf4(-/-) mice also exhibit markedly increased autoantibody production in the B6.C-H-2bm12/KhEg → B6 transfer model of lupus. Although slamf4 function is best characterized in NK cells, the enhanced humoral autoimmunity of B6.Slamf4(-/-) mice is NK cell independent, as judged by depletion studies. Taken together, our findings reveal that slamf4 has an NK cell-independent negative regulatory role in the pathogenesis of lupus a normally non-autoimmune prone genetic background. PMID: 21622868 Funding information This work was supported by: NIAID NIH HHS, United States Grant ID: P01 AI065687-01A1 NIAMS NIH HHS, United States Grant ID: K08AR0578B1 NIAID NIH HHS, United States Grant ID: P01 AI065687 NIAMS NIH HHS, United States Grant ID: K08 AR057861-01 NIAID NIH HHS, United States Grant ID: P01-AI065687 NIDDK NIH HHS, United States Grant ID: P30 DK043351 More Less keyboard_arrow_down