MST1 deficiency promotes B cell responses by CD4+ T cell-derived IL-4, resulting in hypergammaglobulinemia

Biochemical and Biophysical Research Communications
Eunchong ParkTae Sung Kim

Abstract

MST1 deficiency causes T and B cell lymphopenia, resulting in combined immunodeficiency. However, MST1-deficient patients also exhibit autoimmune-like symptoms such as hypergammaglobulinemia and autoantibody production. Recent studies have shown that the autoimmune responses observed in MST1-deficient patients were most likely attributable to defective regulatory T (Treg) cells instead of intrinsic signals in MST1-lacking B cells. Nevertheless, it is not determined how MST1 deficiency in T cells breaks B cell tolerance and causes systemic autoimmune-like phenotypes. In this study, we confirmed that Mst1-/- mice developed hypergammaglobulinemia associated with increased levels of IgG, IgA, and IgE. We also showed that uncontrolled B cell responses were resulted from the IL-4-rich environment created by CD4+ T cells. Defective MST1-FOXO1 signaling down-regulated Treg cells, resulting in the collapse of immune tolerance where the populations of Th2 and T follicular helper cells expanded. In conclusion, we suggest that MST1 acts as a molecular brake to maintain immune tolerance by regulating T cell-mediated B cell activation.

Citations

Feb 21, 2018·Frontiers in Immunology·Jiali ChengChaohong Liu
Jan 7, 2019·Journal of Clinical Immunology·Samin SharafianNima Parvaneh
May 6, 2019·Cells·Takayoshi Yamauchi, Toshiro Moroishi
Mar 31, 2018·Cancers·Zaid TahaXiaolong Yang
Dec 22, 2020·Immunology Letters·Paipai GuoQingtong Wang

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