Poly-ADP-ribosyl polymerase-14 promotes T helper 17 and follicular T helper development

摘要

Transcription factors are critical determinants of T helper cell fate and require a variety of co-factors to activate gene expression. We previously identified the ADP ribosyl-transferase poly-ADP-ribosyl polymerase 14 (PARP-14) as a co-factor of signal transducer and activator of transcription (STAT) 6 that is important in B-cell and T-cell responses to interleukin-4, particularly in the differentiation of T helper type 2 (Th2) cells. However, whether PARP-14 functions during the development of other T helper subsets is not known. In this report we demonstrate that PARP-14 is highly expressed in Th17 cells, and that PARP-14 deficiency and pharmacological blockade of PARP activity result in diminished Th17 differentiation in vitro and in a model of allergic airway inflammation. We further show that PARP-14 is expressed in T follicular helper (Tfh) cells and Tfh cell development is impaired in PARP-14-deficient mice following immunization with sheep red blood cells or inactivated influenza virus. Decreases in Th17 and Tfh development are correlated with diminished phospho-STAT3 and decreased expression of the interleukin-6 receptor a-chain in T cells. Together, these studies demonstrate that PARP-14 regulates multiple cytokine responses during inflammatory immunity.