Non-invasive mechanical ventilation for cystic fibrosis patients--a potential bridge to transplantation

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Abstract
T helper type 17 (Th17) cells secrete IL-17A, IL-17F, IL-21, and IL-22 cytokines and can provide protection against extracellular pathogens or promote certain immune-mediated diseases. The basic leucine zipper transcription factor ATF-like (Batf) contributes to the transcriptional programming of multiple effector T cells but is indispensable for Th17 cell development. Here, we have interrogated mechanisms by which Batf may act to stabilize the Th17 cell phenotype. We find that in vitro differentiated Th17 cells have increased expression of Th1 and Treg signature genes in the absence of Batf. In addition, Batf-deficient (Batf KO) mice succumb to Citrobacter rodentium infection, which correlates with diminished IL-17A and IL-22 cytokine production and increased Foxp3 and Ifng expression compared to WT mice. We find that Batf acts to maintain the Th17 program in long-term Th17 culture conditions by repressing Th1 and Treg programming, at least in part, by antagonizing STAT5 binding to Th1- and Treg-specific genes. Our findings suggest that a function of Batf in Th17 development and maintenance is the antagonism of the actions of STAT5.

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