PMID- 35551270 OWN - NLM STAT- MEDLINE DCOM- 20220701 LR - 20221113 IS - 2042-0226 (Electronic) IS - 1672-7681 (Print) IS - 1672-7681 (Linking) VI - 19 IP - 7 DP - 2022 Jul TI - The kinase p38alpha functions in dendritic cells to regulate Th2-cell differentiation and allergic inflammation. PG - 805-819 LID - 10.1038/s41423-022-00873-2 [doi] AB - 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 p38alpha activity in DCs was decreased upon HDM stimulation and dynamically regulated by both extrinsic signals and Th2-instructive cytokines. p38alpha-specific deletion in cDC1s but not in cDC2s or macrophages promoted Th2 responses under HDM stimulation. Further study showed that p38alpha in cDC1s regulated Th2-cell differentiation by modulating the MK2-c-FOS-IL-12 axis. Importantly, crosstalk between p38alpha-dependent DCs and Th2 cells occurred during the sensitization phase, not the effector phase, and was conserved between mice and humans. Our results identify p38alpha 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. CI - (c) 2022. The Author(s). FAU - Han, Miaomiao AU - Han M AD - ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 200031, Shanghai, China. FAU - Ma, Jingyu AU - Ma J AD - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China. FAU - Ouyang, Suidong AU - Ouyang S AD - Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, 523808, Dongguan, China. FAU - Wang, Yanyan AU - Wang Y AD - Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, 523808, Dongguan, China. FAU - Zheng, Tingting AU - Zheng T AD - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China. AD - Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, 523808, Dongguan, China. FAU - Lu, Peishan AU - Lu P AD - Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, 523808, Dongguan, China. FAU - Zheng, Zihan AU - Zheng Z AD - Biomedical Analysis Center, Army Medical University, 400038, Chongqing, China. FAU - Zhao, Weiheng AU - Zhao W AD - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China. AD - Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China. FAU - Li, Hongjin AU - Li H AD - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China. AD - Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 200437, Shanghai, China. FAU - Wu, Yun AU - Wu Y AD - Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, 523808, Dongguan, China. FAU - Zhang, Baohua AU - Zhang B AD - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China. AD - Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, 200072, Shanghai, China. FAU - Hu, Ran AU - Hu R AD - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China. AD - Basic Department of Cancer Center, Shanghai Tenth People's Hospital of Tongji University, 200072, Shanghai, China. FAU - Otsu, Kinya AU - Otsu K AD - Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan. AD - School of Cardiovascular Medicine and Sciences, King's College London, London, SE59NU, UK. FAU - Liu, Xinguang AU - Liu X AD - Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, 523808, Dongguan, China. FAU - Wan, Ying AU - Wan Y AD - Biomedical Analysis Center, Army Medical University, 400038, Chongqing, China. wanying516@foxmail.com. FAU - Li, Huabin AU - Li H AD - ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 200031, Shanghai, China. allergyli@163.com. FAU - Huang, Gonghua AU - Huang G AUID- ORCID: 0000-0003-1579-5478 AD - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China. gonghua.huang@gdmu.edu.cn. AD - Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, 523808, Dongguan, China. gonghua.huang@gdmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220512 PL - China TA - Cell Mol Immunol JT - Cellular & molecular immunology JID - 101242872 RN - 0 (Cytokines) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 14) SB - IM MH - Animals MH - Cell Differentiation MH - Cytokines/metabolism MH - Dendritic Cells/metabolism MH - Humans MH - *Hypersensitivity/metabolism MH - Inflammation/metabolism MH - Mice MH - Mitogen-Activated Protein Kinase 14/*metabolism MH - *Th2 Cells/metabolism PMC - PMC9243149 OTO - NOTNLM OT - Allergy OT - Th2 OT - dendritic cell OT - p38alpha COIS- The authors declare no competing interests. EDAT- 2022/05/14 06:00 MHDA- 2022/07/02 06:00 PMCR- 2022/05/12 CRDT- 2022/05/13 13:21 PHST- 2021/06/30 00:00 [received] PHST- 2022/04/15 00:00 [accepted] PHST- 2022/04/02 00:00 [revised] PHST- 2022/05/14 06:00 [pubmed] PHST- 2022/07/02 06:00 [medline] PHST- 2022/05/13 13:21 [entrez] PHST- 2022/05/12 00:00 [pmc-release] AID - 10.1038/s41423-022-00873-2 [pii] AID - 873 [pii] AID - 10.1038/s41423-022-00873-2 [doi] PST - ppublish SO - Cell Mol Immunol. 2022 Jul;19(7):805-819. doi: 10.1038/s41423-022-00873-2. Epub 2022 May 12.