Advertisement
ResearchIn-Press PreviewImmunologyPulmonology Open Access | 10.1172/JCI165689
1Division of Intramural Research, NIEHS/NIH, Durham, United States of America
2Department of Nephrology, Duke University Medical Center, Durham, United States of America
Find articles by Li, H. in: JCI | PubMed | Google Scholar
1Division of Intramural Research, NIEHS/NIH, Durham, United States of America
2Department of Nephrology, Duke University Medical Center, Durham, United States of America
Find articles by Bradbury, J. in: JCI | PubMed | Google Scholar
1Division of Intramural Research, NIEHS/NIH, Durham, United States of America
2Department of Nephrology, Duke University Medical Center, Durham, United States of America
Find articles by Edin, M. in: JCI | PubMed | Google Scholar |
1Division of Intramural Research, NIEHS/NIH, Durham, United States of America
2Department of Nephrology, Duke University Medical Center, Durham, United States of America
Find articles by Gruzdev, A. in: JCI | PubMed | Google Scholar |
1Division of Intramural Research, NIEHS/NIH, Durham, United States of America
2Department of Nephrology, Duke University Medical Center, Durham, United States of America
Find articles by Li, H. in: JCI | PubMed | Google Scholar
1Division of Intramural Research, NIEHS/NIH, Durham, United States of America
2Department of Nephrology, Duke University Medical Center, Durham, United States of America
Find articles by Graves, J. in: JCI | PubMed | Google Scholar
1Division of Intramural Research, NIEHS/NIH, Durham, United States of America
2Department of Nephrology, Duke University Medical Center, Durham, United States of America
Find articles by DeGraff, L. in: JCI | PubMed | Google Scholar
1Division of Intramural Research, NIEHS/NIH, Durham, United States of America
2Department of Nephrology, Duke University Medical Center, Durham, United States of America
Find articles by Lih, F. in: JCI | PubMed | Google Scholar
1Division of Intramural Research, NIEHS/NIH, Durham, United States of America
2Department of Nephrology, Duke University Medical Center, Durham, United States of America
Find articles by Feng, C. in: JCI | PubMed | Google Scholar
1Division of Intramural Research, NIEHS/NIH, Durham, United States of America
2Department of Nephrology, Duke University Medical Center, Durham, United States of America
Find articles by Wolf, E. in: JCI | PubMed | Google Scholar
1Division of Intramural Research, NIEHS/NIH, Durham, United States of America
2Department of Nephrology, Duke University Medical Center, Durham, United States of America
Find articles by Bortner, C. in: JCI | PubMed | Google Scholar
1Division of Intramural Research, NIEHS/NIH, Durham, United States of America
2Department of Nephrology, Duke University Medical Center, Durham, United States of America
Find articles by London, S. in: JCI | PubMed | Google Scholar
1Division of Intramural Research, NIEHS/NIH, Durham, United States of America
2Department of Nephrology, Duke University Medical Center, Durham, United States of America
Find articles by Sparks, M. in: JCI | PubMed | Google Scholar |
1Division of Intramural Research, NIEHS/NIH, Durham, United States of America
2Department of Nephrology, Duke University Medical Center, Durham, United States of America
Find articles by Coffman, T. in: JCI | PubMed | Google Scholar
1Division of Intramural Research, NIEHS/NIH, Durham, United States of America
2Department of Nephrology, Duke University Medical Center, Durham, United States of America
Find articles by Zeldin, D. in: JCI | PubMed | Google Scholar
Published March 14, 2024 - More info
In lung, thromboxane A2 (TXA2) activates the TP receptor to induce pro-inflammatory and bronchoconstrictor effects. Thus, TP receptor antagonists and TXA2 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 TXA2 reduces Th9 cell differentiation during allergic lung inflammation. Th9 cells were decreased ~2-fold and airway hyperresponsiveness was attenuated in lungs of allergic mice treated with TXA2. Naïve CD4+ T cell differentiation to Th9 cells and IL-9 production was inhibited dose-dependently by TXA2 in vitro. TP receptor deficient mice had a ~2-fold increase in numbers of Th9 cells in lungs in vivo after OVA exposure compared to wild type (WT) mice. Naïve CD4+ T cells from TP deficient mice exhibited increased Th9 cell differentiation and IL-9 production in vitro compared to CD4+ T cells from WT mice. TXA2 also suppressed Th2 and enhanced Treg differentiation both in vitro and in vivo. Thus, in contrast to its acute, pro-inflammatory effects, TXA2 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.