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

Abstract

Regulatory T cells (Treg) 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, Treg 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 Treg 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.

LRIG1 controls proliferation of adult neural stem cells by facilitating TGFβ and BMP signalling pathways

“…For example, Guimenny et al, used non-neuronal cell lines and C.elegans to discover both direct and genetic interactions between BMPR’s and LRIG1 via a series of immunoprecipitation assays 21 and animal physiology. Additionally, Ferguson et al demonstrated dysregulation in BMP signalling as assessed by SMAD expression via immunostaining and western blotting in a Lrig1 KO glioblastoma cell line and others have begun exploring the TGF β superfamily and LRIG1 in other cell types 33 , 34 .…”