PU.1 expression in T cells is required for the development of IL-9 producing T cells in allergic inflammation (141.14)

Abstract

Abstract The well documented Ets family transcription factor, PU.1 is an important regulator of mast cell, granulocyte and B cell development. Previous studies from our laboratory have identified a novel role for PU.1 in regulating Th2 cell cytokine expression. To further define a role for PU.1 in the development of allergic inflammation in vivo, we studied the development of allergic airway inflammation in mice with a conditional deletion of PU.1 in T cells. Despite the development of normal Th2-responses in the periphery, PU.1 deficient T cells have attenuated allergic inflammation in the lung as compared to wild type mice. To elucidate the mechanism for decreased inflammation in the lung, analysis of cytokines and chemokines from mice that had T cells lacking PU.1, demonstrated significantly decreased levels of IL-9 in the bronchoalveolar lavage fluid concomitant with a significant reduction in the pro-allergic chemokines, CCL17 & CCL22 in lung tissue. We identified PU.1 as a factor that promotes the Th9 phenotype by both repressing Th2 cytokine production and increasing IL-9 production. PU.1 was required for normal generation of IL-9 secreting T cells in vitro and ectopic expression of PU.1 increased IL-9 and chemokine production from Th9 cultures. Together, these data suggest a critical role for PU.1 in generating the Th9 phenotype and in the development of allergic inflammation.