MST1 deficiency promotes B cell responses by CD4(+) T cell-derived IL-4, resulting in hypergammaglobulinemia
- Authors
- Park, Eunchong; Kim, Myun Soo; Song, Ju Han; Roh, Kyung-Hye; Lee, Rana; Kim, Tae Sung
- Issue Date
- 15-7월-2017
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Keywords
- MST1; CD4(+) T cell; B cell activation; IL-4; CD40L
- Citation
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.489, no.1, pp.56 - 62
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Volume
- 489
- Number
- 1
- Start Page
- 56
- End Page
- 62
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/82825
- DOI
- 10.1016/j.bbrc.2017.05.094
- ISSN
- 0006-291X
- 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. (C) 2017 Elsevier Inc. All rights reserved.
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Collections - Graduate School > Department of Life Sciences > 1. Journal Articles
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