ADAM9 enhances Th17 cell differentiation and autoimmunity by activating TGF-β1
Masataka Umeda, Nobuya Yoshida, Ryo Hisada, Catalina Burbano, Seo Yeon K. Orite, Michihito Kono, Vasileios C. Kyttaris, Suzanne Krishfield, Caroline A. Owen, George C. Tsokos
Abstract
Significance Members of the ADAM family of proteinases are expressed by immune cells and have been postulated to contribute to the development of autoimmune pathology. The current report provides evidence that ADAM9 drives the development of Th17 cells by producing bioactive TGF-β1. ADAM9 deficiency mitigates experimental autoimmune encephalomyelitis in mice, while T cells from patients with systemic lupus erythematosus express increased amounts of ADAM9, which, when suppressed, mitigates the generation of Th17 cells. The findings of this study identify the pivotal role of ADAM9 in the development of Th17 cells, and its targeting should ameliorate pathology in Th17-dependent diseases.