dc.contributor.author | Toki, Shinji | |
dc.contributor.author | Goleniewska, Kasia | |
dc.contributor.author | Zhang, Jian | |
dc.contributor.author | Zhou, Weisong | |
dc.contributor.author | Newcomb, Dawn C. | |
dc.contributor.author | Zhou, Baohua | |
dc.contributor.author | Kita, Hirohito | |
dc.contributor.author | Boyd, Kelli L. | |
dc.contributor.author | Peebles, Ray S., Jr. | |
dc.date.accessioned | 2020-10-22T19:30:02Z | |
dc.date.available | 2020-10-22T19:30:02Z | |
dc.date.issued | 2020-02 | |
dc.identifier.citation | Toki, S., Goleniewska, K., Zhang, J., Zhou, W., Newcomb, D. C., Zhou, B., Kita, H., Boyd, K. L., & Peebles, R. S., Jr (2020). TSLP and IL-33 reciprocally promote each other's lung protein expression and ILC2 receptor expression to enhance innate type-2 airway inflammation. Allergy, 75(7), 1606–1617. https://doi.org/10.1111/all.14196 | en_US |
dc.identifier.issn | 0105-4538 | |
dc.identifier.uri | http://hdl.handle.net/1803/16247 | |
dc.description.abstract | Background The epithelial cell-derived danger signal mediators thymic stromal lymphopoietin (TSLP) and IL-33 are consistently associated with adaptive Th2 immune responses in asthma. In addition, TSLP and IL-33 synergistically promoted group 2 innate lymphoid cell (ILC2) activation to induce innate allergic inflammation. However, the mechanism of this synergistic ILC2 activation is unknown.
Methods BALB/c WT and TSLP receptor-deficient (TSLPR-/-) mice were challenged intranasally with Alternaria extract (Alt-Ext) or PBS for 4 consecutive days to evaluate innate airway allergic inflammation. WT mice pre-administered with rTSLP or vehicle, TSLPR-/- mice, and IL-33 receptor-deficient (ST2(-/-)) mice were challenged intranasally with Alt-Ext or vehicle once or twice to evaluate IL-33 release and TSLP expression in the lung. TSLPR and ST2 expression on lung ILC2 were measured by flow cytometry after treatment of rTSLP, rIL-33, rTSLP + rIL-33, or vehicle.
Results Thymic stromal lymphopoietin receptor deficient mice had significantly decreased the number of lung ILC2 expressing IL-5 and IL-13 following Alt-Ext-challenge compared to WT mice. Further, eosinophilia, protein level of lung IL-4, IL-5, and IL-13, and airway mucus score were also significantly decreased in TSLPR-/- mice compared to WT mice. Endogenous and exogenous TSLP increased Alt-Ext-induced IL-33 release into BALF, and ST2 deficiency decreased Alt-Ext-induced TSLP expression in the lung. Further, rTSLP and rIL-33 treatment reciprocally increased each other's receptor expression on lung ILC2 in vivo and in vitro.
Conclusion Thymic stromal lymphopoietin and IL-33 signaling reciprocally enhanced each other's protein release and expression in the lung following Alt-Ext-challenge and each other's receptor expression on lung ILC2 to enhance ILC2 activation. | en_US |
dc.description.sponsorship | NIH, Grant/Award Number: R01AI111820, R01AI124456, R01AI145265, R21AI145397 and U19AI095227; U.S. Department of Veterans Affairs, Grant/Award Number: I01BX004299 | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Allergy | en_US |
dc.rights | Copyright © 2020 The Authors. Allergy published by John Wiley & Sons Ltd
This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. | |
dc.source.uri | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354889/ | |
dc.subject | Group 2 innate lymphoid cells (ILC2 | en_US |
dc.subject | Group 2 innate lymphoid cells (ILC2) | en_US |
dc.subject | IL-33 | en_US |
dc.subject | TSLP | en_US |
dc.title | TSLP and IL-33 reciprocally promote each other's lung protein expression and ILC2 receptor expression to enhance innate type-2 airway inflammation | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1111/all.14196 | |