title: TPL2 mediates autoimmune inflammation through activation of the TAK1 axis of IL-17 signaling.
abstract: Development of autoimmune diseases, such as multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), involves the inflammatory action of Th1 and Th17 cells, but the underlying signaling mechanism is incompletely understood. We show that the kinase TPL2 is a crucial mediator of EAE and is required for the pathological action of Th17 cells. TPL2 serves as a master kinase mediating the activation of multiple downstream pathways stimulated by the Th17 signature cytokine IL-17. TPL2 acts by linking the IL-17 receptor signal to the activation of TAK1, which involves a dynamic mechanism of TPL2-TAK1 interaction and TPL2-mediated phosphorylation and catalytic activation of TAK1. These results suggest that TPL2 mediates TAK1 axis of IL-17 signaling, thereby promoting autoimmune neuroinflammation.
authors: Department of Immunology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors: Yichuan
authors: Y
authors: Xiao
authors: Department of Immunology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors: Jin
authors: J
authors: Jin
authors: Department of Immunology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors: Mikyoung
authors: M
authors: Chang
authors: Department of Immunology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors: Mako
authors: M
authors: Nakaya
authors: Department of Immunology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors: Hongbo
authors: H
authors: Hu
authors: Department of Immunology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors: Qiang
authors: Q
authors: Zou
authors: Department of Immunology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors: Xiaofei
authors: X
authors: Zhou
authors: Department of Immunology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors: George C
authors: GC
authors: Brittain
authors: Department of Immunology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors: Xuhong
authors: X
authors: Cheng
authors: Department of Immunology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030 The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030 ssun@mdanderson.org.
authors: Shao-Cong
authors: SC
authors: Sun
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D002490:Central Nervous System / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology / Q000473:pathology; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D006413:Hematopoietic System / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000473:pathology*; D020381:Interleukin-17 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D020930:MAP Kinase Kinase Kinases / Q000172:deficiency / Q000378:metabolism*; D018345:Mice, Knockout; D010766:Phosphorylation; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000378:metabolism*; D011836:Radiation Tolerance; D015398:Signal Transduction / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D020381:Interleukin-17; D020930:MAP Kinase Kinase Kinases; D011518:Proto-Oncogene Proteins; D000099151:MAP Kinase Kinase Kinase 7; C489843:Map3k8 protein, mouse