Lrig1-expression confers suppressive function to CD4+ cells and is essential for averting autoimmunity via the Smad2/3/Foxp3 axis
Jae‐Seung Moon, Chun-Chang Ho, Jong‐Hyun Park, Kyungsoo Park, Boyoung Shin, Su-Hyeon Lee, Inês Sequeira, Chin Hee Mun, Jin-Su Shin, Jung-Ho Kim, Beom Seok Kim, Jin-Wook Noh, Eui-Seon Lee, Ji Young Son, Yuna Kim, Yeji lee, Hee Cho, S.Y. So, Jiyoon Park, Eun-Su Choi, Jong‐Won Oh, Sang‐Won Lee, Tomohiro Morio, Fiona M. Watt, Rho Hyun Seong, Sang‐Kyou Lee, Rho Hyun Seong, Sang‐Kyou Lee, Sang‐Kyou Lee
Abstract
Abstract Regulatory T cells (T reg ) are CD4 + T cells with immune-suppressive function, which is defined by Foxp3 expression. However, the molecular determinants defining the suppressive population of T cells have yet to be discovered. Here we report that the cell surface protein Lrig1 is enriched in suppressive T cells and controls their suppressive behaviors. Within CD4 + T cells, T reg cells express the highest levels of Lrig1, and the expression level is further increasing with activation. The Lrig1 + subpopulation from T helper (Th) 17 cells showed higher suppressive activity than the Lrig1 - subpopulation. Lrig1-deficiency impairs the suppressive function of T reg cells, while Lrig1-deficient naïve T cells normally differentiate into other T cell subsets. Adoptive transfer of CD4 + Lrig1 + T cells alleviates autoimmune symptoms in colitis and lupus nephritis mouse models. A monoclonal anti-Lrig1 antibody significantly improves the symptoms of experimental autoimmune encephalomyelitis. In conclusion, Lrig1 is an important regulator of suppressive T cell function and an exploitable target for treating autoimmune conditions.