TAGAP instructs Th17 differentiation by bridging Dectin activation to EPHB2 signaling in innate antifungal response

Jianwen Chen, Ruirui He, Wanwei Sun (), Ru Gao, Qianwen Peng, Liwen Zhu, Yanyun Du, Xiaojian Ma, Xiaoli Guo, Huazhi Zhang, Chengcheng Tan, Junhan Wang, Wei Zhang, Xiufang Weng, Jianghong Man, Hermann Bauer, Qing K. Wang, Bradley N. Martin, Cun-Jin Zhang (), Xiaoxia Li and Chenhui Wang ()
Additional contact information
Jianwen Chen: Huazhong University of Science and Technology
Ruirui He: Huazhong University of Science and Technology
Wanwei Sun: Huazhong University of Science and Technology
Ru Gao: Huazhong University of Science and Technology
Qianwen Peng: Huazhong University of Science and Technology
Liwen Zhu: Nanjing University
Yanyun Du: Huazhong University of Science and Technology
Xiaojian Ma: Huazhong University of Science and Technology
Xiaoli Guo: Huazhong University of Science and Technology
Huazhi Zhang: Huazhong University of Science and Technology
Chengcheng Tan: Huazhong University of Science and Technology
Junhan Wang: University-Affiliated Hospital, Huazhong University of Science and Technology
Wei Zhang: Huazhong University of Science and Technology
Xiufang Weng: Huazhong University of Science and Technology
Jianghong Man: National Center of Biomedical Analysis
Hermann Bauer: Max Planck Institute for Molecular Genetics
Qing K. Wang: Huazhong University of Science and Technology
Bradley N. Martin: Harvard Medical School
Cun-Jin Zhang: Nanjing University
Xiaoxia Li: Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic
Chenhui Wang: Huazhong University of Science and Technology

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract The TAGAP gene locus has been linked to several infectious diseases or autoimmune diseases, including candidemia and multiple sclerosis. While previous studies have described a role of TAGAP in T cells, much less is known about its function in other cell types. Here we report that TAGAP is required for Dectin-induced anti-fungal signaling and proinflammatory cytokine production in myeloid cells. Following stimulation with Dectin ligands, TAGAP is phosphorylated by EPHB2 at tyrosine 310, which bridges proximal Dectin-induced EPHB2 activity to downstream CARD9-mediated signaling pathways. During Candida albicans infection, mice lacking TAGAP mount defective immune responses, impaired Th17 cell differentiation, and higher fungal burden. Similarly, in experimental autoimmune encephalomyelitis model of multiple sclerosis, TAGAP deficient mice develop significantly attenuated disease. In summary, we report that TAGAP plays an important role in linking Dectin-induced signaling to the promotion of effective T helper cell immune responses, during both anti-fungal host defense and autoimmunity.

Date: 2020
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DOI: 10.1038/s41467-020-15564-7

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