SHP-1 regulates STAT6 phosphorylation and IL-4-mediated function in a cell type-specific manner

SHP-1 has been shown to play positive and negative regulatory roles in IL-4-induced STAT6 phosphorylation and in IL-4-mediated functions. To determine whether SHP-1 can regulate STAT6 phosphorylation and IL-4-mediated functions in a cell type-specific manner in the immune system, we examined the IL-4 receptor (IL-4R) expression, STAT6 phosphorylation, and IL-4-mediated functions in CD4 ⁺ and CD8 ⁺ T cells of viable motheaten (me ^v/me ^v) and littermate control (+/-) mice. CD4 ⁺ T cells as well as CD8 ⁺ T cells from the lymph node of me ^v/me ^v and +/- mice expressed comparable levels of IL-4R. In CD4 ⁺ T cells, the loss of SHP-1 activity did not affect IL-4-induced STAT6 phosphorylation or IL-4-mediated function. In contrast, SHP-1-deficient CD8 ⁺ T cells from me ^v/me ^v mice failed to develop into IL-4-producing type-2 cytotoxic T cells (Tc2) in the presence of IL-4 despite that they showed comparable levels of STAT6 phosphorylation to that of +/- CD8 ⁺ T cells. Loss of SHP-1 activity also abolished IL-4-mediated inhibition of c-kit expression in bone marrow-derived mast cell (BMMC). Thus, our data suggest that SHP-1 may regulate IL-4-induced STAT6 phosphorylation and IL-4-mediated functions in a cell type-specific manner.