J Immunol 2009,
PMID: 19542468
Staschke, Kirk A; Dong, Sucai; Saha, Joy; Zhao, Jingyong; Brooks, Nathan A; Hepburn, Deena L; Xia, Jinqi; Gulen, Muhammet F; Kang, Zizhen; Altuntas, Cengiz Z; Tuohy, Vincent K; Gilmour, Raymond; Li, Xiaoxia; Na, Songqing
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.
Diseases/Pathways annotated by Medline MESH: Encephalomyelitis, Autoimmune, Experimental
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Text Mining Data
IL-1/TLR → IL-1R associated kinase 4 (IRAK4): "
The
IL-1R associated kinase 4 (IRAK4) is
critical for
IL-1/TLR signaling
"
IL-1/TLR → IL-1R associated kinase 4 (IRAK4): "
The IL-1R associated kinase 4 (IRAK4) is critical for IL-1/TLR signaling
"
STAT3 → IL-23: "
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
"
STAT3 → IRAK4: "
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
"
STAT3 → IL-23R: "
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
"
IL-23 → IRAK4: "
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
"
IL-23 → IL-23R: "
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
"
IL-23R → IRAK4: "
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
"
IRAK4 → IL-1: "
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
"
IL-23R → IRAK4: "
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
"
Manually curated Databases
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