Lrig1-expression confers suppressive function to CD4⁺ cells and is essential for averting autoimmunity via the Smad2/3/Foxp3 axis.

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.