| First Author | Park E | Year | 2017 |
| Journal | Biochem Biophys Res Commun | Volume | 489 |
| Issue | 1 | Pages | 56-62 |
| PubMed ID | 28527887 | Mgi Jnum | J:251417 |
| Mgi Id | MGI:6103135 | Doi | 10.1016/j.bbrc.2017.05.094 |
| Citation | Park E, et al. (2017) MST1 deficiency promotes B cell responses by CD4(+) T cell-derived IL-4, resulting in hypergammaglobulinemia. Biochem Biophys Res Commun 489(1):56-62 |
| abstractText | 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. |
