title: Poly-ADP-ribosyl polymerase-14 promotes T helper 17 and follicular T helper development.
abstract: 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 α-chain in T cells. Together, these studies demonstrate that PARP-14 regulates multiple cytokine responses during inflammatory immunity.
authors.affiliation: Department of Pediatrics, HB Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.|Department of Integrative and Cellular Physiology, Indiana University-Purdue University, Indianapolis, IN, USA.
authors.forename: Purvi
authors.initials: P
authors.lastname: Mehrotra
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Purna
authors.initials: P
authors.lastname: Krishnamurthy
authors.affiliation: Department of Pediatrics, HB Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.|Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Pediatrics, HB Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.|Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Shreevrat
authors.initials: S
authors.lastname: Goenka
authors.affiliation: Department of Pediatrics, HB Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.|Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012756:Sheep; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D058504:Th17 Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; D050796:STAT3 Transcription Factor; C522628:Parp14 protein, mouse; D011065:Poly(ADP-ribose) Polymerases
keywords: T helper cell; differentiation; knockout; transcription factor