Notch2-dependent GATA3+ Treg cells alleviate allergic rhinitis by suppressing the Th2 cell response.

Autor: Jiao WE; Department of Otolaryngology-Head and Neck Surgery, Central Laboratory, Renmin Hospital of Wuhan University, 238 Jie-Fang Road, Wuhan, Hubei 430060, PR China., Xu S; Department of Otolaryngology-Head and Neck Surgery, Central Laboratory, Renmin Hospital of Wuhan University, 238 Jie-Fang Road, Wuhan, Hubei 430060, PR China., Qiao YL; Department of Otolaryngology-Head and Neck Surgery, Central Laboratory, Renmin Hospital of Wuhan University, 238 Jie-Fang Road, Wuhan, Hubei 430060, PR China., Kong YG; Department of Otolaryngology-Head and Neck Surgery, Central Laboratory, Renmin Hospital of Wuhan University, 238 Jie-Fang Road, Wuhan, Hubei 430060, PR China., Sun L; Department of Otolaryngology-Head and Neck Surgery, General Hospital of The Central Theater Command, Wuhan 430070, Hubei, PR China., Deng YQ; Department of Otolaryngology-Head and Neck Surgery, Central Laboratory, Renmin Hospital of Wuhan University, 238 Jie-Fang Road, Wuhan, Hubei 430060, PR China., Yang R; Department of Otolaryngology-Head and Neck Surgery, Central Laboratory, Renmin Hospital of Wuhan University, 238 Jie-Fang Road, Wuhan, Hubei 430060, PR China., Tao ZZ; Department of Otolaryngology-Head and Neck Surgery, Central Laboratory, Renmin Hospital of Wuhan University, 238 Jie-Fang Road, Wuhan, Hubei 430060, PR China; Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, 238 Jie-Fang Road, Wuhan, Hubei 430060, PR China., Hua QQ; Department of Otolaryngology-Head and Neck Surgery, Central Laboratory, Renmin Hospital of Wuhan University, 238 Jie-Fang Road, Wuhan, Hubei 430060, PR China; Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, 238 Jie-Fang Road, Wuhan, Hubei 430060, PR China. Electronic address: hqqrm@sina.com., Chen SM; Department of Otolaryngology-Head and Neck Surgery, Central Laboratory, Renmin Hospital of Wuhan University, 238 Jie-Fang Road, Wuhan, Hubei 430060, PR China; Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, 238 Jie-Fang Road, Wuhan, Hubei 430060, PR China. Electronic address: shimingchen0468@163.com.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2022 Nov; Vol. 112, pp. 109261. Date of Electronic Publication: 2022 Sep 22.
DOI: 10.1016/j.intimp.2022.109261
Abstrakt: The aim of this study was to investigate the role and mechanism of Notch2-dependent GATA3+ Treg cells in allergic rhinitis (AR). Samples were collected from patients in the control and AR groups to detect differences in the numbers of GATA3+ Treg cells and their intracellular Notch2 levels. The effects of Notch2 on GATA3+ Treg cell differentiation and function in vitro were detected. AR mice were subjected to adoptive transfer of GATA3+ Treg cells to detect changes in the allergic inflammatory response and Th2 cells. Mice with Treg cell-specific knockout of Notch2 were constructed, and an AR model was established to detect the changes. The number of GATA3+ Treg cells and intracellular Notch2 expression in peripheral blood of the AR group were decreased compared with the controls (P < 0.05), and the number of GATA3+ Treg cells was significantly negatively correlated with the level of allergen-specific IgE (sIgE; P < 0.01). In vitro experiments showed that Notch2 promoted the differentiation and immunosuppressive function of GATA3+ Treg cells, and Notch2 directly promoted GATA3 transcription in Treg cells (P < 0.05). Animal experiments indicated that adoptive transfer of GATA3+ Treg cells reduced the allergic inflammatory response in AR mice (P < 0.05). The number of GATA3+ Treg cells was decreased in gene knockout mice (P < 0.05), and autoimmune inflammation was observed. After modeling, the allergic inflammatory response was further aggravated (P < 0.05). Overall, our findings indicate that Notch2 alleviates AR by specifically increasing GATA3+ Treg cell differentiation. Notch2 expressed in Treg cells is expected to be a new therapeutic target for AR.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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