Other
14 Authors
- Dong S,
- Kang Z,
- Xia J,
- Gulen MF,
- Gilmour R,
- Hepburn DL,
- Zhao J,
- Tuohy VK,
- Altuntas CZ,
- Li X,
- Na S,
- Brooks NA,
- Saha J,
- Staschke KA
| First Author | Staschke KA | Year | 2009 |
| Journal | J Immunol | Volume | 183 |
| Issue | 1 | Pages | 568-77 |
| PubMed ID | 19542468 | Mgi Jnum | J:149967 |
| Mgi Id | MGI:3849492 | Doi | 10.4049/jimmunol.0802361 |
| Citation | Staschke KA, et al. (2009) IRAK4 kinase activity is required for Th17 differentiation and Th17-mediated disease. J Immunol 183(1):568-77 |
| abstractText | Both IL-23- and IL-1-mediated signaling pathways play important roles in Th17 cell differentiation, cytokine production, and autoimmune diseases. The IL-1R-associated kinase 4 (IRAK4) is critical for IL-1/TLR signaling. We show here that inactivation of IRAK4 kinase in mice (IRAK4 KI) results in significant resistance to experimental autoimmune encephalomyelitis due to a reduction in infiltrating inflammatory cells into the CNS and reduced Ag-specific CD4(+) T cell-mediated IL-17 production. Adoptive transfer of myelin oligodendrocyte glycoprotein 35-55-specific IRAK4 KI Th17 cells failed to induce experimental autoimmune encephalomyelitis in either wild-type or IRAK4 KI recipient mice, indicating the lack of autoantigen-specific Th17 cell activities in the absence of IRAK4 kinase activity. Furthermore, the absence of IRAK4 kinase activity blocked induction of IL-23R expression, STAT3 activation by IL-23, and Th17 cytokine expression in differentiated Th17 cells. Importantly, blockade of IL-1 signaling by IL-1RA inhibited Th17 differentiation and IL-23-induced cytokine expression in differentiated Th17 cells. The results of these studies demonstrate that IL-1-mediated IRAK4 kinase activity in T cells is essential for induction of IL-23R expression, Th17 differentiation, and autoimmune disease. |
