The phosphatase MKP-1 is known as a negative regulator of innate immune responses induced by Toll-like receptor signaling in macrophages. In Immunity, Chi and colleagues show that induction of MKP-1 by pathogen-recognition receptors in DCs controls the reciprocal development of T helper type 1 cells and IL-17-producing helper T cells. MKP-1-deficient DCs induce a greater frequency of IL-17+ T cells and a lower frequency of interferon-γ-positive T cells in vitro and in vivo without affecting the survival or proliferation of T cells or the expression of type 2 cytokines. The authors show that MKP-1 inhibits activation of the kinase p38 and subsequently modulates the expression of IL-12 and IL-6 in DCs. In addition, MKP-1 inhibits TGF-β expression and the generation of inducible regulatory T cells. Thus, MKP-1 acts in DCs to integrate innate stimuli to regulate the differentiation of T helper type 1 cells, IL-17-producing helper T cells and inducible regulatory T cells.

Immunity 35, 45–58 (2011)