Journal
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Volume 187, Issue 8, Pages 812-822Publisher
AMER THORACIC SOC
DOI: 10.1164/rccm.201211-2073OC
Keywords
T helper cell type 9 cells; cyclooxygenase 2; asthma; prostaglandins; IL-17RB
Categories
Funding
- National Institutes of Health/National Institute of Environmental Health Sciences, Division of Intramural Research [Z01 ES025043, Z01 ES050167]
Ask authors/readers for more resources
Rationale: Helper CD4(+) T cell subsets, including IL-9-and IL-10-producing T helper cell type 9 (Th9) cells, exist under certain inflammatory conditions. Cyclooxygenase (COX)-1 and COX-2 play important roles in allergic lung inflammation and asthma. It is unknown whether COX-derived eicosanoids regulate Th9 cells during allergic lung inflammation. Objectives: To determine the role of COX metabolites in regulating Th9 cell differentiation and function during allergic lung inflammation. Methods: COX-1(-/-), COX-2(-/-), and wild-type (WT) mice were studied in an in vivo model of ovalbumin-induced allergic inflammation and an in vitro model of Th9 differentiation using flow cytometry, cytokine assays, confocal microscopy, real-time PCR, and immunoblotting. In addition, the role of specific eicosanoids and their receptors was examined using synthetic prostaglandins (PGs), selective inhibitors, and siRNA knockdown. Measurements and Main Results: Experimental endpoints were not different between COX-1(-/-) and WT mice; however, the percentage of IL-9(+) CD4(+) T cells was increased in lung, bronchoalveolar layage fluid, lymph nodes, and blood of allergic COX-2(-/-) mice relative to WT. Bronchoalyeolar lavage fluid IL-9 and IL-10, serum IL-9, and lung IL-17RB levels were significantly increased in allergic COX-2(-/-) mice or in WT mice treated with COX-2 inhibitors. IL-9, IL-10, and IL-17RB expression in vivo was inhibited by PGD(2) and PGE(2), which also reduced Th9 cell differentiation of murine and human naive CD4(+) T cells in vitro. Inhibition of protein kinase A significantly increased Th9 cell differentiation of naive CD4(+) T cells isolated from WT mice in vitro. Conclusions: COX-2-derived PGD(2) and PGE(2) regulate Th9 cell differentiation by suppressing IL-17RB expression via a protein kinase A-dependent mechanism.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available