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

AI Article Synopsis

  • * The study identifies the cell surface protein Lrig1 as a key factor in enhancing the suppressive abilities of Tregs, particularly in T helper (Th) 17 cells.
  • * Lrig1 deficiency leads to weakened suppressive functions but does not stop the differentiation of naïve T cells; targeting Lrig1 could be a potential therapeutic strategy for autoimmune diseases, as shown by improved outcomes in mouse models.

Article Abstract

Regulatory T cells (T) 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 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 cells, while Lrig1-deficient naïve T cells normally differentiate into other T cell subsets. Adoptive transfer of CD4Lrig1 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10477202PMC
http://dx.doi.org/10.1038/s41467-023-40986-4DOI Listing

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