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

Eunchong Park, Myun Soo Kim, Ju Han Song, Kyung Hye Roh, Rana Lee, Tae Sung Kim

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)56-62
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume489
Issue number1
DOIs
Publication statusPublished - 2017 Jul 15

Fingerprint

Hypergammaglobulinemia
T-cells
Interleukin-4
B-Lymphocytes
Cells
T-Lymphocytes
Regulatory T-Lymphocytes
Immune Tolerance
Lymphopenia
Helper-Inducer T-Lymphocytes
Autoimmunity
Brakes
Autoantibodies
Immunoglobulin A
Immunoglobulin E
Immunoglobulin G
Chemical activation
Phenotype
Population

Keywords

  • B cell activation
  • CD40L
  • CD4 T cell
  • IL-4
  • MST1

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

MST1 deficiency promotes B cell responses by CD4+ T cell-derived IL-4, resulting in hypergammaglobulinemia. / Park, Eunchong; Kim, Myun Soo; Song, Ju Han; Roh, Kyung Hye; Lee, Rana; Kim, Tae Sung.

In: Biochemical and Biophysical Research Communications, Vol. 489, No. 1, 15.07.2017, p. 56-62.

Research output: Contribution to journalArticle

Park, Eunchong ; Kim, Myun Soo ; Song, Ju Han ; Roh, Kyung Hye ; Lee, Rana ; Kim, Tae Sung. / MST1 deficiency promotes B cell responses by CD4+ T cell-derived IL-4, resulting in hypergammaglobulinemia. In: Biochemical and Biophysical Research Communications. 2017 ; Vol. 489, No. 1. pp. 56-62.
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