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Prostaglandin I?promotes the development of IL-17-producing ?? T cells that associate with the epithelium during allergic lung inflammation.


ABSTRACT: ?? T cells rapidly produce cytokines and represent a first line of defense against microbes and other environmental insults at mucosal tissues and are thus thought to play a local immunoregulatory role. We show that allergic airway inflammation was associated with an increase in innate IL-17-producing ?? T (??-17) cells that expressed the ?E?7 integrin and were closely associated with the airway epithelium. Importantly, PGI(2) and its receptor IP, which downregulated airway eosinophilic inflammation, promoted the emergence of these intraepithelial ??-17 cells into the airways by enhancing IL-6 production by lung eosinophils and dendritic cells. Accordingly, a pronounced reduction of ??-17 cells was observed in the thymus of naive mice lacking the PGI(2) receptor IP, as well as in the lungs during allergic inflammation, implying a critical role for PGI(2) in the programming of "natural" ??-17 cells. Conversely, iloprost, a stable analog of PGI(2), augmented IL-17 production by ?? T cells but significantly reduced airway inflammation. Together, these findings suggest that PGI(2) plays a key immunoregulatory role by promoting the development of innate intraepithelial ??-17 cells through an IL-6-dependent mechanism. By enhancing ??-17 cell responses, stable analogs of PGI(2) may be exploited in the development of new immunotherapeutic approaches.

SUBMITTER: Jaffar Z 

PROVIDER: S-EPMC3208053 | BioStudies | 2011-01-01

REPOSITORIES: biostudies

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