| First Author | Johnson DJ | Year | 2013 |
| Journal | J Exp Med | Volume | 210 |
| Issue | 7 | Pages | 1419-31 |
| PubMed ID | 23797092 | Mgi Jnum | J:274967 |
| Mgi Id | MGI:6207382 | Doi | 10.1084/jem.20122239 |
| Citation | Johnson DJ, et al. (2013) Shp1 regulates T cell homeostasis by limiting IL-4 signals. J Exp Med 210(7):1419-31 |
| abstractText | The protein-tyrosine phosphatase Shp1 is expressed ubiquitously in hematopoietic cells and is generally viewed as a negative regulatory molecule. Mutations in Ptpn6, which encodes Shp1, result in widespread inflammation and premature death, known as the motheaten (me) phenotype. Previous studies identified Shp1 as a negative regulator of TCR signaling, but the severe systemic inflammation in me mice may have confounded our understanding of Shp1 function in T cell biology. To define the T cell-intrinsic role of Shp1, we characterized mice with a T cell-specific Shp1 deletion (Shp1fl/fl CD4-cre). Surprisingly, thymocyte selection and peripheral TCR sensitivity were unaltered in the absence of Shp1. Instead, Shp1(fl/fl) CD4-cre mice had increased frequencies of memory phenotype T cells that expressed elevated levels of CD44. Activation of Shp1-deficient CD4(+) T cells also resulted in skewing to the Th2 lineage and increased IL-4 production. After IL-4 stimulation of Shp1- deficient T cells, Stat 6 activation was sustained, leading to enhanced Th2 skewing. Accordingly, we observed elevated serum IgE in the steady state. Blocking or genetic deletion of IL-4 in the absence of Shp1 resulted in a marked reduction of the CD44hi population. Therefore, Shp1 is an essential negative regulator of IL-4 signaling in T lymphocytes. |
