机构：[1]ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 200031 Shanghai, China[2]Shanghai Institute of Immunology, Shanghai Jiao TongUniversity School of Medicine, 200025 Shanghai, China[3]Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, 523808Dongguan, China[4]Biomedical Analysis Center, Army Medical University, 400038 Chongqing, China[5]Department of Cardiovascular Medicine, Graduate School of Medicine,Osaka University, Osaka 565-0871, Japan[6]School of Cardiovascular Medicine and Sciences, King’s College London, London SE59NU, UK[7]Tongji Hospital, TongjiMedical College, Huazhong University of Science and Technology, 430030 Wuhan, China华中科技大学同济医学院附属同济医院[8]Department of Dermatology, Yueyang Hospital of IntegratedTraditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 200437 Shanghai, China[9]Department of Clinical LaboratoryMedicine, Shanghai Tenth People’s Hospital of Tongji University, 200072 Shanghai, China[10]Basic Department of Cancer Center, Shanghai Tenth People’sHospital of Tongji University, 200072 Shanghai, China
Dendritic cells (DCs) play a critical role in controlling T helper 2 (Th2) cell-dependent diseases, but the signaling mechanism that triggers this function is not fully understood. We showed that p38 alpha activity in DCs was decreased upon HDM stimulation and dynamically regulated by both extrinsic signals and Th2-instructive cytokines. p38 alpha-specific deletion in cDC1s but not in cDC2s or macrophages promoted Th2 responses under HDM stimulation. Further study showed that p38 alpha in cDC1s regulated Th2-cell differentiation by modulating the MK2-c-FOS-IL-12 axis. Importantly, crosstalk between p38 alpha-dependent DCs and Th2 cells occurred during the sensitization phase, not the effector phase, and was conserved between mice and humans. Our results identify p38 alpha signaling as a central pathway in DCs that integrates allergic and parasitic instructive signals with Th2-instructive cytokines from the microenvironment to regulate Th2-cell differentiation and function, and this finding may offer a novel strategy for the treatment of allergic diseases and parasitic infection.
基金：
National Natural Science Foundation of China [91642104, 31670897, 81471528, 81600788, 81671399, 81971329, 81725004, 82001702]; Guangdong Basic and Applied Basic Research Foundation [2021B1515130004, 2021B1515140021]; National Key R&D Program of China [2018YFC0115900]
第一作者机构：[1]ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 200031 Shanghai, China
共同第一作者：
通讯作者：
通讯机构：[2]Shanghai Institute of Immunology, Shanghai Jiao TongUniversity School of Medicine, 200025 Shanghai, China[3]Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, 523808Dongguan, China
推荐引用方式(GB/T 7714)：
Miaomiao Han,Jingyu Ma,Suidong Ouyang,et al.The kinase p38 alpha functions in dendritic cells to regulate Th2-cell differentiation and allergic inflammation[J].CELLULAR & MOLECULAR IMMUNOLOGY.2022,19(7):805-819.doi:10.1038/s41423-022-00873-2.
APA：
Miaomiao Han,Jingyu Ma,Suidong Ouyang,Yanyan Wang,Tingting Zheng...&Gonghua Huang.(2022).The kinase p38 alpha functions in dendritic cells to regulate Th2-cell differentiation and allergic inflammation.CELLULAR & MOLECULAR IMMUNOLOGY,19,(7)
MLA：
Miaomiao Han,et al."The kinase p38 alpha functions in dendritic cells to regulate Th2-cell differentiation and allergic inflammation".CELLULAR & MOLECULAR IMMUNOLOGY 19..7(2022):805-819
医学