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Dendrobium nobile protects against ovalbumin-induced allergic rhinitis by regulating intestinal flora and suppressing lung inflammation

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Chinese Journal of Natural Medicines 2022年第6期20卷 443-457页

作者： DUAN Fei-Peng LI Yi-Sheng HU tian-Yong PAN Xin-Quan MA Fang FENG Yue QIU Shu-Qi ZHENG Yi-Qing Institute of Otolaryngology Institute of Hearing and Speech of Sun Yat-sen UniversitySun Yat-sen Me-morial HospitalSun Yat-sen UniversityGuangzhou 510520China Department of Otolaryngology Longgang E.N.T hospital&Shenzhen Key Laboratory of E.N.TInstitute of E.N.TShenzhen 518172China

Antibiotic exposure-induced dysbiosis of the intestinal flora increases the risk of developing allergic rhinitis.Hence,regulating the balance of intestinal flora may be useful for preventing and treating allergic rhinitis.However,the underlying mechanism is unclear.Dendrobium nobile(Shihu)exhibits anti-inflammatory and immune activities.Hence,in this study,we investigated the mechanism via which Shihu may improve allergic rhinitis.Mouse models of allergic rhinitis with intestinal flora dysbiosis(Model-D,antibiotics induce intestinal flora dysbiosis with ovalbumin-induced allergy)and normal intestinal flora with allergic rhinitis(Model-N,ovalbumin-induced allergy)were established.the effect of Shihu on intestinal flora and inflammation caused during allergic rhinitis were analyzed.Allergic symptoms,infiltration of hematoxylin and eosin in the lungs and nose,and the release of various factors[interleukin(IL)-2,IL-4,IFN-y,IL-6,IL-10,and IL-17]in the lungs were evaluated.the results indicate that intestinal flora dysbiosis exacerbated lung and nose inflammation in allergic rhinitis.However,treatment with the Shihu extract effectively reversed these symp-toms.Besides,the Shihu extract inhibited the PI3K/AXt/mtOR pathway and increased the level of Forkhead box protein in the lungs.Additionally,the Shihu extract reversed intestinal flora dysbiosis at the phylum and genus levels and improved Regulator T cell differentiation.Furthermore,in the Model-D group,the Shihu extract inhibited the decrease in the diversity and abundance of the intestinal flora.Screening was performed to determine which intestinal flora was positively correlated with treg differentiation using Spearman5 s correlation analysis.In conclusion,we showed that Shihu extract restored the balance in intestinal flora and ameliorated inflammation in the lungs of allergic rhinitis mice and predicted a therapeutic new approach using traditional Chinese Medicine to improve allergic rhinitis.

关键词： Dendrobium nobile(Shihu) Allergic rhinitis Intestinal flora Regulator T cell Inflammation

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Ubiquitin-specific peptidase 18 regulates the differentiation and function of treg cells

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Genes & Diseases 2021年第3期8卷 344-352页

作者： Lu Yang Yukai Jing Danqing Kang Panpan Jiang Na Li Xinrong Zhou Yan Chen Lisa S.Westerberg Chaohong Liu Department of Pathogen Biology Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei Province430030PR China Department of Immunology School of MedicineYangtze UniversityJingzhouHubei Province434023PR China Department of Endocrinology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei Province430030PR China the Second Department of Pediatrics Affiliated Hospital of Zunyi Medical UniversityZunyiGuiZhou Province563000PR China Department of Microbiology tumor and cell Biology Karolinska InstitutetStockholm17177Sweden

Ubiquitin-specific peptidase 18(USP18)plays an important role in the development of CD11b^(+)dendritic cells(DCs)and th17 cells,however,its role in the differentiation of other t cell subsets,especially in regulatory t(treg)cells,is unknown.In our study,we used Usp18 K0 mice to study the loss of USP18 on the impact of treg cell differentiation and function.We found that USP18 deficiency upregulates the differentiation of treg cells,which may lead to disrupted homeostasis of peripheral t cells,and downregulates INF-y,IL-2,IL-17A producing CD4^(+)t cells and INF-γproducing CD8^(+)t cells.Mechanistically,we also found that the upre-gulation of tregs is due to elevated expression of CD25 in Usp18 KO mice.Finally,we found that the suppressive function of Usp18 KO tregs is downregulated.Altogether,our study was the first to identify the role of USP18 in tregs differentiation and its suppressive function,which may provide a new reference for the treatment of treg function in many autoimmune diseases,and USP18 can be used as a new therapeutic target for precise medical treatment.

关键词： CD25 Foxp3 ICOS Regulator T cell USP18

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