Th9 cells regulate mast cell recruitment in acute allergic lung inflammation (57.12)

Abstract

Abstract Th2 cells are classically thought to contribute to the pathogenesis of asthma. IL-9, long described as a Th2 cytokine has also been shown to mediate allergic inflammation in both human and murine studies. Recently, we have identified an ETS-family transcription factor PU.1 required for generating the Th9 phenotype and in the development of allergic inflammation. Mice with a conditional deletion of PU.1 in T cells demonstrated attenuated allergic inflammation concomitant with decreased levels of IL-9. IL-9 is also well documented to play an important role in mast cell growth and differentiation. To determine if Th9 cells are required for the recruitment of mast cells in vivo, we examined mast cell infiltration in the lung in mice with blocking IL-9 antibodies as well as in mice with PU.1 deficient T cells. Both experiments with either blockade of IL-9 or PU.1 deficient T cells demonstrated diminished mast cell numbers in the lung. We further examined the effect of transferred Th2 and Th9 cells on mast cell recruitment. Transfer of differentiated Th2 or Th9 cells from D011.10 mice to wild type mice demonstrate that while Th2 cells increase mast cells, as detected by expression of mast cell proteases in the lung by 4-fold, recipients of Th9 cells had over 11-fold increased expression. Therefore, our studies suggest an important role for Th9 cells in mast cell recruitment in models of acute allergic inflammation.