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Notch Signaling Promotes Development of Allergic Rhinitis by Suppressing Foxp3 Expression and Treg Cell Differentiation.
Int Arch Allergy Immunol. 2019; 178(1):33-44.IA

Abstract

BACKGROUND

The Notch signaling pathway plays an important role in regulating human immune function, but the relationship between allergic rhinitis (AR) and Notch signaling remains unclear.

OBJECTIVE

To investigate the role of Notch signaling in the pathogenesis of AR and its regulation on Foxp3-Treg cells.

METHOD

The sera of 100 patients with AR and 50 controls were collected to assess the differences in Notch1, Jagged1, and DLL1 (Delta-like 1) expression. Experimental mice were divided into normal control, AR, Notch inhibitor, and dexamethasone groups. Allergic symptoms, total IgE levels, and the proportion of Treg cells in the peripheral blood were detected. Notch1, Jagged1, NICD (Notch intracellular domain, also known as ICN), and Foxp3 expression and Th1/Th2/Th17-related cytokines in the spleen were detected and compared between each group of mice.

RESULTS

Compared with the control group, the expression of Notch1 and Jagged1 in patients with AR was significantly elevated (p < 0.05). The expression of Notch1 and Jagged1 in patients with severe AR was higher than that observed in the mild to moderate AR patients and positively correlated with the levels of allergen sIgE (p < 0.05). The animal experiments revealed that compared with the normal control group, the expression of Notch1, Jagged1, and NICD in the AR group was increased, Foxp3 expression was decreased, and the proportion of Treg cells was decreased (p < 0.05). Compared with the AR group, allergic symptoms and total serum IgE levels and the expression of Notch1, Jagged1, and NICD were significantly decreased in the Notch inhibited group, whereas the expression of Foxp3 and the proportion of Treg cells were increased significantly (p < 0.05). The Th2-type immune responses were also enhanced and Th1-type immune responses decreased in the AR group, but the Th1/Th2 imbalance was reversed in the Notch inhibited group.

CONCLUSION

Notch signaling downregulates Foxp3 expression and inhibits the differentiation of Treg cells to promote the development of AR. Blocking Notch signaling may be a potential treatment for AR.

Authors+Show Affiliations

Department of Otolaryngology, Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.Department of Otolaryngology, First College of Clinical Medical Science, Three Gorges University, Yichang, China. Department of Otorhinolaryngology, Yichang Central People's Hospital, Yichang, China.Department of Otolaryngology, Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.Department of Otolaryngology, Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China. Institute of Otolaryngology, Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.Department of Otolaryngology, Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China. Institute of Otolaryngology, Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.Department of Otolaryngology, Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China, shimingchen0468@163.com. Institute of Otolaryngology, Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China, shimingchen0468@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30391960

Citation

Jiao, Wo-Er, et al. "Notch Signaling Promotes Development of Allergic Rhinitis By Suppressing Foxp3 Expression and Treg Cell Differentiation." International Archives of Allergy and Immunology, vol. 178, no. 1, 2019, pp. 33-44.
Jiao WE, Wei JF, Kong YG, et al. Notch Signaling Promotes Development of Allergic Rhinitis by Suppressing Foxp3 Expression and Treg Cell Differentiation. Int Arch Allergy Immunol. 2019;178(1):33-44.
Jiao, W. E., Wei, J. F., Kong, Y. G., Xu, Y., Tao, Z. Z., & Chen, S. M. (2019). Notch Signaling Promotes Development of Allergic Rhinitis by Suppressing Foxp3 Expression and Treg Cell Differentiation. International Archives of Allergy and Immunology, 178(1), 33-44. https://doi.org/10.1159/000493328
Jiao WE, et al. Notch Signaling Promotes Development of Allergic Rhinitis By Suppressing Foxp3 Expression and Treg Cell Differentiation. Int Arch Allergy Immunol. 2019;178(1):33-44. PubMed PMID: 30391960.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Notch Signaling Promotes Development of Allergic Rhinitis by Suppressing Foxp3 Expression and Treg Cell Differentiation. AU - Jiao,Wo-Er, AU - Wei,Jin-Feng, AU - Kong,Yong-Gang, AU - Xu,Yu, AU - Tao,Ze-Zhang, AU - Chen,Shi-Ming, Y1 - 2018/11/02/ PY - 2018/06/19/received PY - 2018/08/28/accepted PY - 2018/11/6/pubmed PY - 2019/4/11/medline PY - 2018/11/5/entrez KW - Allergic rhinitis KW - Foxp3 KW - Notch intracellular domain KW - Notch signal KW - Treg cells SP - 33 EP - 44 JF - International archives of allergy and immunology JO - Int. Arch. Allergy Immunol. VL - 178 IS - 1 N2 - BACKGROUND: The Notch signaling pathway plays an important role in regulating human immune function, but the relationship between allergic rhinitis (AR) and Notch signaling remains unclear. OBJECTIVE: To investigate the role of Notch signaling in the pathogenesis of AR and its regulation on Foxp3-Treg cells. METHOD: The sera of 100 patients with AR and 50 controls were collected to assess the differences in Notch1, Jagged1, and DLL1 (Delta-like 1) expression. Experimental mice were divided into normal control, AR, Notch inhibitor, and dexamethasone groups. Allergic symptoms, total IgE levels, and the proportion of Treg cells in the peripheral blood were detected. Notch1, Jagged1, NICD (Notch intracellular domain, also known as ICN), and Foxp3 expression and Th1/Th2/Th17-related cytokines in the spleen were detected and compared between each group of mice. RESULTS: Compared with the control group, the expression of Notch1 and Jagged1 in patients with AR was significantly elevated (p < 0.05). The expression of Notch1 and Jagged1 in patients with severe AR was higher than that observed in the mild to moderate AR patients and positively correlated with the levels of allergen sIgE (p < 0.05). The animal experiments revealed that compared with the normal control group, the expression of Notch1, Jagged1, and NICD in the AR group was increased, Foxp3 expression was decreased, and the proportion of Treg cells was decreased (p < 0.05). Compared with the AR group, allergic symptoms and total serum IgE levels and the expression of Notch1, Jagged1, and NICD were significantly decreased in the Notch inhibited group, whereas the expression of Foxp3 and the proportion of Treg cells were increased significantly (p < 0.05). The Th2-type immune responses were also enhanced and Th1-type immune responses decreased in the AR group, but the Th1/Th2 imbalance was reversed in the Notch inhibited group. CONCLUSION: Notch signaling downregulates Foxp3 expression and inhibits the differentiation of Treg cells to promote the development of AR. Blocking Notch signaling may be a potential treatment for AR. SN - 1423-0097 UR - https://www.unboundmedicine.com/medline/citation/30391960/Notch_Signaling_Promotes_Development_of_Allergic_Rhinitis_by_Suppressing_Foxp3_Expression_and_Treg_Cell_Differentiation_ L2 - https://www.karger.com?DOI=10.1159/000493328 DB - PRIME DP - Unbound Medicine ER -