ILC2 frequency and activity are inhibited by glucocorticoid treatment via STAT pathway in patients with asthma

• Published in: Allergy (Copenhagen) Vol. 73; no. 9; pp. 1860 - 1870
• Main Authors: Yu, Q. N., Guo, Y. B., Li, X., Li, C. L., Tan, W. P., Fan, X. L., Qin, Z. L., Chen, D., Wen, W. P., Zheng, S. G., Fu, Q. L.
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01-09-2018; John Wiley and Sons Inc
• Subjects: Adult; Allergic diseases; Allergic rhinitis; Anti-Asthmatic Agents - pharmacology; Anti-Asthmatic Agents - therapeutic use; Asthma; Asthma - diagnosis; Asthma - drug therapy; Asthma - immunology; Asthma - metabolism; asthma patient; Cytokines - metabolism; Data processing; Female; glucocorticoid; Glucocorticoids; Glucocorticoids - pharmacology; Glucocorticoids - therapeutic use; group 2 innate lymphoid cells; Humans; Immunity, Innate; Immunoglobulin E - immunology; inhibition; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Lymphocyte Count; Lymphocyte Subsets - immunology; Lymphocyte Subsets - metabolism; Lymphoid cells; Male; Middle Aged; Monocytes; Original; ORIGINAL ARTICLES; Patients; Peripheral blood; Respiratory Function Tests; Rhinitis; Signal transduction; Signal Transduction - drug effects; STAT signalling pathway; STAT Transcription Factors - metabolism; Stat3 protein; Stat5 protein; Stat6 protein; Treatment Outcome; Young Adult; inhibition; glucocorticoid; STAT signalling pathway; group 2 innate lymphoid cells; asthma patient
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/all.13438

Background
Group 2 innate lymphoid cells (ILC2s) were closely associated with asthma. However, there were no perspective studies about the effects of glucocorticoid on ILC2s in asthma patients. Our objective was to perform a perspective study and evaluate the ILC2 activity after glucocorticoid therapy in asthma patients.
Methods
The asthma and asthma with allergic rhinitis patients were treated with glucocorticoid for 3 months. The circulating ILC2 levels were evaluated. The effects of glucocorticoid on ILC2s and possible signalling pathways were investigated in vitro.
Results
The patients were well‐controlled, and the high ILC2 levels were significantly decreased at 1 and 3 months after treatment. Peripheral blood monocytes from allergic patients produced dramatic IL‐5, IL‐13 and IL‐9 in response to IL‐25, IL‐33 plus IL‐2, and glucocorticoid significantly decreased their levels. Moreover, ILC2s were identified to be the predominant source of IL‐5, IL‐13 and IL‐9, and glucocorticoid treatment was able to reverse their high levels. STAT3, STAT5, STAT6, JAK3 and MEK signalling pathways were proved to be involved in regulating ILC2 activity under the glucocorticoid treatment.
Conclusion
The data suggested that glucocorticoid administration could be effective in treating asthma by regulating ILC2s via MEK/JAK‐STAT signalling pathways. This provides a new understanding of glucocorticoid application in regard to allergic diseases.
High circulating ILC2s were found in asthma and asthma with allergic rhinitis patients, and significantly decreased after treatment of glucocorticoid. High levels of IL‐5, IL‐13 and IL‐9 in response to epithelium‐derived cytokines were mostly produced by the increased ILC2s from asthma patients. Glucocorticoid treatment is able to reverse the high levels of IL‐5 and IL‐13 produced by ILC2s via STAT3, STAT5 and STAT6 signalling pathways.