- Title
- Severe asthma ILC2s demonstrate enhanced proliferation that is modified by biologics
- Creator
- Malik, Bilal; Bartlett, Nathan W.; Upham, John W.; Nichol, Kristy S.; Harrington, John; Wark, Peter A. B.
- Relation
- Respirology Vol. 28, Issue 8, p. 758-766
- Publisher Link
- http://dx.doi.org/10.1111/resp.14506
- Publisher
- John Wiley & Sons
- Resource Type
- journal article
- Date
- 2023
- Description
- Background and Objective: Type 2 (T2) innate lymphoid cells (ILC2s) contribute to airway inflammation and disease in asthma. We hypothesize that ILC2s isolated from people with severe allergic and eosinophilic asthma would exhibit an enhanced T2 inflammatory activity that would be altered following treatment with mepolizumab and omalizumab. We compare peripheral blood (PB) isolated ILC2's proliferative capacity, IL-5 and IL-13 secretion and phenotype between healthy without asthma (HC), non-asthma allergic (NAA), mild asthma (MA) and severe allergic and eosinophilic asthma (SA) subjects. We then determined the impact of 6 months treatment with either mepolizumab or omalizumab on ILC2s physiology of SA subjects. Methods: ILC2s were sorted and cultured in the presence of IL-2, IL-25, IL-33 and thymic stromal lymphopoietin (TSLP) for 14 days. ILC2s proliferation, phenotypes and functions were assessed using flowcytometry. The ILC2s response was then reassessed following clinically successful treatment of SA subjects with mepolizumab and omalizumab. Results: SA ILC2s demonstrated increased proliferative capacity, TSLP receptor (TSLPR), GATA3 and NFATc1 protein expressions and increased IL-5 and IL-13 release. ILC2s were also capable of releasing IL-6 in response to stimulation. Mepolizumab treatment reduced ILC2s proliferative capacity and expression of TSLPR, GATA3 and NFATc1. Both mepolizumab and omalizumab were associated with reduced ILC2s release of IL-5 and IL-13, only mepolizumab reduced IL-6. Conclusion: ILC2s from severe allergic and eosinophilic asthma demonstrated an active phenotype typified by increased proliferation, TSLPR, GATA3 and NFATc1 expression and increased IL-5, IL-13 and IL-6 release. Mepolizumab reduced markers of ILC2s activation.
- Subject
- innate lymphoid cells (ILC2); mepolizumab; omalizumab; proliferation; severe asthma; thymic stromal lymphopoietin receptor; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1482039
- Identifier
- uon:50840
- Identifier
- ISSN:1323-7799
- Rights
- © 2023 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. (http://creativecommons.org/licenses/by/4.0/).
- Language
- eng
- Full Text
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