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Poly‐ADP‐ribosyl polymerase‐14 promotes T helper 17 and follicular T helper development
Author(s) -
Mehrotra Purvi,
Krishnamurthy Purna,
Sun Jie,
Goenka Shreevrat,
Kaplan Mark H.
Publication year - 2015
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12515
Subject(s) - biology , stat protein , stat3 , t helper cell , cytokine , immunology , t cell , transcription factor , microbiology and biotechnology , cancer research , signal transduction , immune system , gene , genetics
Summary 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‐ STAT 3 and decreased expression of the interleukin‐6 receptor α ‐chain in T cells. Together, these studies demonstrate that PARP ‐14 regulates multiple cytokine responses during inflammatory immunity.