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

Abstract

<jats:title>Abstract</jats:title><jats:p>Regulatory T cells (T<jats:sub>reg</jats:sub>) are CD4<jats:sup>+</jats:sup> 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<jats:sup>+</jats:sup> T cells, T<jats:sub>reg</jats:sub> cells express the highest levels of Lrig1, and the expression level is further increasing with activation. The Lrig1<jats:sup>+</jats:sup> subpopulation from T helper (Th) 17 cells showed higher suppressive activity than the Lrig1<jats:sup>-</jats:sup> subpopulation. Lrig1-deficiency impairs the suppressive function of T<jats:sub>reg</jats:sub> cells, while Lrig1-deficient naïve T cells normally differentiate into other T cell subsets. Adoptive transfer of CD4<jats:sup>+</jats:sup>Lrig1<jats:sup>+</jats:sup> 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.</jats:p>