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Notch2 suppresses the development of allergic rhinitis by promoting FOXP3 expression and Treg cell differentiation.
- Source :
-
Life sciences [Life Sci] 2021 Nov 01; Vol. 284, pp. 119922. Date of Electronic Publication: 2021 Sep 01. - Publication Year :
- 2021
-
Abstract
- Aims: Notch signaling is closely related to a variety of diseases, but the role of Notch2 in allergic rhinitis (AR) remain unclear. This study was performed to investigate the effects of Notch2 on the differentiation of Treg cells and on the inflammatory response of AR.<br />Materials and Methods: Peripheral blood (including 101 AR patients and 66 Controls) and nasal mucosa (including 19 AR patients and 17 Controls) were collected to detect the expression levels of Notch2, NICD2 and FOXP3. CD4+ T cells of human origin were selected to detect the effects of Notch2 on the differentiation of Treg cells and FOXP3. An AR mouse model was established, and lentiviruses overexpressing Notch2 were administered. Then, allergic symptoms, OVA-sIgE titers, nasal mucosal inflammation, Th1/Th2/Th17 cytokines and splenic Treg cells were assessed.<br />Key Findings: Compared with that in the Control group, the expression of Notch2 in the AR group was decreased, and Notch2 expression was negatively correlated with the degree of allergy (P < 0.01). The expression levels of Notch2, NICD2 and FOXP3 were decreased in the nasal mucosa of AR patients. Notch2 can promote the differentiation of human Treg cells in vitro (P < 0.05), and Notch2 can directly promote FOXP3 transcription. Animal experiments showed after the upregulation of Notch2 expression, the allergic inflammatory of mice with AR was reduced, the differentiation of Treg cells was increased, and the imbalance of T cells was reversed (P < 0.05).<br />Significance: Notch2 promotes the differentiation of Treg cells by upregulating FOXP3 expression, thus significantly inhibiting the inflammatory response of AR.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Female
Forkhead Transcription Factors genetics
Humans
Inflammation pathology
Lentivirus metabolism
Mice, Inbred C57BL
Nasal Mucosa metabolism
Nasal Mucosa pathology
Receptor, Notch2 blood
Rhinitis, Allergic blood
Severity of Illness Index
Transcription, Genetic
Mice
Cell Differentiation
Forkhead Transcription Factors metabolism
Receptor, Notch2 metabolism
Rhinitis, Allergic immunology
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0631
- Volume :
- 284
- Database :
- MEDLINE
- Journal :
- Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 34480930
- Full Text :
- https://doi.org/10.1016/j.lfs.2021.119922