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The Journal of Immunology, 2002, 169: 5997-6004.
Copyright © 2002 by The American Association of Immunologists

A Key Role for Prostaglandin I2 in Limiting Lung Mucosal Th2, But Not Th1, Responses to Inhaled Allergen1

Zeina Jaffar2, Kong-Sang Wan2 and Kevan Roberts3

Medical Specialities, Southampton General Hospital, Southampton, United Kingdom

The cellular events that serve to regulate lung mucosal Th2 responses and limit allergic inflammatory reactions are unclear. Using the DO11.10 TCR transgenic mouse, we developed a model of T cell-mediated pulmonary inflammation and demonstrated that high levels of PGI2 are produced in the airways following OVA inhalation. Selective inhibition of cyclooxygenase-2 in vivo specifically reduced PGI2 synthesis and resulted in a marked increase in Th2-mediated, but not Th1-mediated, lung inflammation. The elevated Th2-mediated inflammatory response elicited by the cyclooxygenase-2 inhibitor was associated with enhanced airway hyperreactivity and was coincident with a marked increase in the levels of IL-4, IL-5, and IL-13 in the airways, but a reduction in IL-10 production. In keeping with these observations, we found that the mRNA for the PGI2 receptor was expressed by Th2, but not Th1, cells, and transcripts for the PGI2 receptor were induced by IL-4 and OVA peptide stimulation. Interestingly, treatment with PGI2 or its stable analog, carbaprostacyclin, augmented IL-10 production by Th2 cells. Collectively, our findings reveal a key role for PGI2 in differentially limiting Th2 responses, possibly by promoting production of the immunosuppressive cytokine IL-10 at the site of allergic lung inflammation. These results indicate an important role for prostanoids generated during inflammation in regulating mucosal T cell responses and highlight a potential risk in the use of cyclooxygenase-2-specific inhibitors by allergic asthmatics.




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