Interleukin-10 Production by Th1 Cells Requires Interleukin-12-Induced STAT4 Transcription Factor and ERK MAP Kinase Activation by High Antigen Dose

Abstract

SummaryCD4+ T cells producing interleukin-10 (IL-10) and interferon-γ (IFN-γ) are reported in chronic infections. However, the signals that direct the development of IL-10-producing T helper 1 (Th1) cells are undefined. We showed that development of IL-10-producing Th1 cells required high T cell receptor (TCR) ligation, sustained ERK1 and ERK2 MAP kinases phosphorylation, and IL-12-induced STAT4 transcription factor activation. Repeated TCR triggering led to enhanced IL-10 production by Th1 cells, and continued IL-12 action and high-dose TCR signaling were required for the development and maintenance of IL-10-producing Th1 cells. Although Th1, Th2, and Th17 cells require the activation of distinct STATs for their differentiation, activation of ERK1 and ERK2 was a common requirement for production of IL-10 by all Th cell subsets. IL-10 expression also correlated with c-maf expression. Despite having distinct functions in protection against pathogens, all Th cells share the important task of controlling overexuberant immune responses by means of IL-10 production.

Cord-Blood-Derived Mesenchymal Stromal Cells Downmodulate CD4+T-Cell Activation by Inducing IL-10-Producing Th1 Cells

“…+ T-cells that has been described recently [16,18,[22][23][24]. We also observed an effect of MSCs on the expression profile of resting CD4…”

SHP-1–Pyk2–Src Protein Complex and p38 MAPK Pathways Independently Regulate IL-10 Production in Lipopolysaccharide-Stimulated Macrophages

“…p38 MAPK regulates IL-10 production in both control and SHP-1-null splenic macrophages ERK has been shown to regulate IL-10 production in murine Th1 cells and macrophages (58)(59)(60)(61)(62). p38 MAPK also plays a critical ) were treated with PP2 (0.1-1 mM) for 2 h prior to LPS (10 mg/ml) stimulation for 24 h and IL-10 production was determined by ELISA.…”

CD26-Mediated Induction of EGR2 and IL-10 as Potential Regulatory Mechanism for CD26 Costimulatory Pathway

“…CD46 costimulation induces interaction of the cytoplasmic tail of CD46 (CYT-1-BC1) with SPAK, leading to sustained phosphorylation of ERK1/2 (45). The importance of sustained phosphorylation of ERK1/2 has also been reported for the development of IL-10-producing Th1 cells (46). However, sustained phosphorylation of ERK1/2 alone is not sufficient to explain the preferential IL-10 production, and transcription factors such as c-Maf, IRF4, Blimp-1, GATA-3, and E4BP4 (NFIL3) may be associated with the transcription of IL-10 (34-38).…”