PMID- 34169075 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210626 IS - 2296-634X (Print) IS - 2296-634X (Electronic) IS - 2296-634X (Linking) VI - 9 DP - 2021 TI - Allergen-Specific Treg Cells Upregulated by Lung-Stage S. japonicum Infection Alleviates Allergic Airway Inflammation. PG - 678377 LID - 10.3389/fcell.2021.678377 [doi] LID - 678377 AB - Schistosoma japonicum infection showed protective effects against allergic airway inflammation (AAI). However, controversial findings exist especially regarding the timing of the helminth infection and the underlying mechanisms. Most previous studies focused on understanding the preventive effect of S. japonicum infection on asthma (infection before allergen sensitization), whereas the protective effects of S. japonicum infection (allergen sensitization before infection) on asthma were rarely investigated. In this study, we investigated the protective effects of S. japonicum infection on AAI using a mouse model of OVA-induced asthma. To explore how the timing of S. japonicum infection influences its protective effect, the mice were percutaneously infected with cercaria of S. japonicum at either 1 day (infection at lung-stage during AAI) or 14 days before ovalbumin (OVA) challenge (infection at post-lung-stage during AAI). We found that lung-stage S. japonicum infection significantly ameliorated OVA-induced AAI, whereas post-lung-stage infection did not. Mechanistically, lung-stage S. japonicum infection significantly upregulated the frequency of regulatory T cells (Treg cells), especially OVA-specific Treg cells, in lung tissue, which negatively correlated with the level of OVA-specific immunoglobulin E (IgE). Depletion of Treg cells in vivo partially counteracted the protective effect of lung-stage S. japonicum infection on asthma. Furthermore, transcriptomic analysis of lung tissue showed that lung-stage S. japonicum infection during AAI shaped the microenvironment to favor Treg induction. In conclusion, our data showed that lung-stage S. japonicum infection could relieve OVA-induced asthma in a mouse model. The protective effect was mediated by the upregulated OVA-specific Treg cells, which suppressed IgE production. Our results may facilitate the discovery of a novel therapy for AAI. CI - Copyright (c) 2021 Li, Zhang, Luo, Li, Yang, Zhu, Wu, Wang, Sun, Xie, Xu, Wang, Qian, Chen, Wan and Hu. FAU - Li, Zhidan AU - Li Z AD - NHC Key Laboratory of Parasite and Vector Biology (National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention), Shanghai, China. FAU - Zhang, Wei AU - Zhang W AD - State Key Laboratory of Genetic Engineering, Ministry of Education Key Laboratory of Contemporary Anthropology, Human Phenome Institute, Fudan University, Shanghai, China. AD - Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai, China. FAU - Luo, Fang AU - Luo F AD - State Key Laboratory of Genetic Engineering, Ministry of Education Key Laboratory of Contemporary Anthropology, Human Phenome Institute, Fudan University, Shanghai, China. AD - Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai, China. FAU - Li, Jian AU - Li J AD - State Key Laboratory of Genetic Engineering, Ministry of Education Key Laboratory of Contemporary Anthropology, Human Phenome Institute, Fudan University, Shanghai, China. AD - Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai, China. AD - Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China. FAU - Yang, Wenbin AU - Yang W AD - State Key Laboratory of Genetic Engineering, Ministry of Education Key Laboratory of Contemporary Anthropology, Human Phenome Institute, Fudan University, Shanghai, China. AD - Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai, China. FAU - Zhu, Bingkuan AU - Zhu B AD - State Key Laboratory of Genetic Engineering, Ministry of Education Key Laboratory of Contemporary Anthropology, Human Phenome Institute, Fudan University, Shanghai, China. AD - Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai, China. FAU - Wu, Qunfeng AU - Wu Q AD - State Key Laboratory of Genetic Engineering, Ministry of Education Key Laboratory of Contemporary Anthropology, Human Phenome Institute, Fudan University, Shanghai, China. AD - Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai, China. FAU - Wang, Xiaoling AU - Wang X AD - NHC Key Laboratory of Parasite and Vector Biology (National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention), Shanghai, China. FAU - Sun, Chengsong AU - Sun C AD - State Key Laboratory of Genetic Engineering, Ministry of Education Key Laboratory of Contemporary Anthropology, Human Phenome Institute, Fudan University, Shanghai, China. AD - Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai, China. FAU - Xie, Yuxiang AU - Xie Y AD - State Key Laboratory of Genetic Engineering, Ministry of Education Key Laboratory of Contemporary Anthropology, Human Phenome Institute, Fudan University, Shanghai, China. AD - Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai, China. FAU - Xu, Bin AU - Xu B AD - NHC Key Laboratory of Parasite and Vector Biology (National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention), Shanghai, China. FAU - Wang, Zhaojun AU - Wang Z AD - Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Qian, Feng AU - Qian F AD - State Key Laboratory of Genetic Engineering, Ministry of Education Key Laboratory of Contemporary Anthropology, Human Phenome Institute, Fudan University, Shanghai, China. AD - Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai, China. FAU - Chen, Jiaxu AU - Chen J AD - NHC Key Laboratory of Parasite and Vector Biology (National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention), Shanghai, China. FAU - Wan, Yanmin AU - Wan Y AD - Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China. AD - Department of Radiology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. FAU - Hu, Wei AU - Hu W AD - NHC Key Laboratory of Parasite and Vector Biology (National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention), Shanghai, China. AD - State Key Laboratory of Genetic Engineering, Ministry of Education Key Laboratory of Contemporary Anthropology, Human Phenome Institute, Fudan University, Shanghai, China. AD - Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai, China. AD - Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China. LA - eng PT - Journal Article DEP - 20210608 PL - Switzerland TA - Front Cell Dev Biol JT - Frontiers in cell and developmental biology JID - 101630250 PMC - PMC8217774 OTO - NOTNLM OT - Schistosoma infection OT - Treg OT - allergic airway inflammation OT - asthma OT - helminth therapy OT - parasite-host interaction COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/06/26 06:00 MHDA- 2021/06/26 06:01 PMCR- 2021/01/01 CRDT- 2021/06/25 06:54 PHST- 2021/03/09 00:00 [received] PHST- 2021/04/22 00:00 [accepted] PHST- 2021/06/25 06:54 [entrez] PHST- 2021/06/26 06:00 [pubmed] PHST- 2021/06/26 06:01 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fcell.2021.678377 [doi] PST - epublish SO - Front Cell Dev Biol. 2021 Jun 8;9:678377. doi: 10.3389/fcell.2021.678377. eCollection 2021.