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attenuates allergic lung inflammation through regulation of Th2, Th9, and Treg differentiation
- Source :
- Journal of Clinical Investigation. May, 2024, Vol. 134 Issue 9
- Publication Year :
- 2024
-
Abstract
- In lung, thromboxane [A.sub.2] ([TXA.sub.2]) activates the TP receptor to induce proinflammatory and bronchoconstrictor effects. Thus, TP receptor antagonists and [TXA.sub.2] synthase inhibitors have been tested as potential asthma therapeutics in humans. Th9 cells play key roles in asthma and regulate the lung immune response to allergens. Herein, we found that [TXA.sub.2] reduces Th9 cell differentiation during allergic lung inflammation. Th9 cells were decreased approximately 2-fold and airway hyperresponsiveness was attenuated in lungs of allergic mice treated with [TXA.sub.2]. Naive [CD4.sup.+] T cell differentiation to Th9 cells and IL-9 production were inhibited dose-dependently by [TXA.sub.2] in vitro. TP receptor-deficient mice had an approximately 2-fold increase in numbers of Th9 cells in lungs in vivo after OVA exposure compared with wild-type mice. Naive [CD4.sup.+] T cells from TP- deficient mice exhibited increased Th9 cell differentiation and IL-9 production in vitro compared with [CD4.sup.+] T cells from wild-type mice. [TXA.sub.2] also suppressed Th2 and enhanced Treg differentiation both in vitro and in vivo. Thus, in contrast to its acute, proinflammatory effects, [TXA.sub.2] also has longer-lasting immunosuppressive effects that attenuate the Th9 differentiation that drives asthma progression. These findings may explain the paradoxical failure of anti-thromboxane therapies in the treatment of asthma.<br />Introduction Development of allergic lung inflammation is a complex process involving both immune and inflammatory events. In the immune phase, allergens are taken up and processed by antigen-presenting cells such [...]
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 134
- Issue :
- 9
- Database :
- Gale General OneFile
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.794866128
- Full Text :
- https://doi.org/10.1172/JCI165689