| First Author | Fukaya T | Year | 2014 |
| Journal | Biochem Biophys Res Commun | Volume | 447 |
| Issue | 3 | Pages | 471-8 |
| PubMed ID | 24732356 | Mgi Jnum | J:219458 |
| Mgi Id | MGI:5620855 | Doi | 10.1016/j.bbrc.2014.04.012 |
| Citation | Fukaya T, et al. (2014) Loss of Sprouty4 in T cells ameliorates experimental autoimmune encephalomyelitis in mice by negatively regulating IL-1beta receptor expression. Biochem Biophys Res Commun 447(3):471-8 |
| abstractText | Th17 cells, which have been implicated in autoimmune diseases, require IL-6 and TGF-beta for early differentiation. To gain pathogenicity, however, Th17 cells require IL-1beta and IL-23. The underlying mechanism by which these confer pathogenicity is not well understood. Here we show that Sprouty4, an inhibitor of the PLCgamma-ERK pathway, critically regulates inflammatory Th17 (iTh17) cell differentiation. Sprouty4-deficient mice, as well as mice adoptively transferred with Sprouty4-deficient T cells, were resistant to experimental autoimmune encephalitis (EAE) and showed decreased Th17 cell generation in vivo. In vitro, Sprouty4 deficiency did not severely affect TGF-beta/IL-6-induced Th17 cell generation but strongly impaired Th17 differentiation induced by IL-1/IL-6/IL-23. Analysis of Th17-related gene expression revealed that Sprouty4-deficient Th17 cells expressed lower levels of IL-1R1 and IL-23R, while RORgammat levels were similar. Consistently, overexpression of Sprouty4 or pharmacological inhibition of ERK upregulated IL-1R1 expression in primary T cells. Thus, Sprouty4 and ERK play a critical role in developing iTh17 cells in Th17 cell-driven autoimmune diseases. |
