Poly-ADP ribose polymerase-14 limits severity of allergic skin disease

dc.contributor.authorKrishnamurthy, Purna
dc.contributor.authorDa-Silva-Arnold, Sonia
dc.contributor.authorTurner, Matthew J.
dc.contributor.authorTravers, Jeffrey B.
dc.contributor.authorKaplan, Mark H.
dc.contributor.departmentDepartment of Pediatrics, IU School of Medicineen_US
dc.date.accessioned2017-08-11T17:05:55Z
dc.date.available2017-08-11T17:05:55Z
dc.date.issued2017
dc.description.abstractPoly-ADP ribose polymerase-14 (PARP14 or ARTD8) was initially identified as a transcriptional co-activator for signal transducer and activator of transcription 6 (Stat6), where the presence of interleukin-4 (IL-4) and activated Stat6 induces the enzymatic activity of PARP14 that promotes T helper type 2 differentiation and allergic airway disease. To further our understanding of PARP14 in allergic disease, we studied the function of PARP14 in allergic inflammation of skin using mice that express constitutively active Stat6 in T cells (Stat6VT) and develop spontaneous inflammation of the skin. We mated Stat6VT mice to Parp14−/− mice and observed that approximately 75% of the Stat6VT × Parp14−/− mice develop severe atopic dermatitis (AD)-like lesions, compared with about 50% of Stat6VT mice, and have increased morbidity compared with Stat6VT mice. Despite this, gene expression in the skin and the cellular infiltrates was only modestly altered by the absence of PARP14. In contrast, we saw significant changes in systemic T-cell cytokine production. Moreover, adoptive transfer experiments demonstrated that decreases in IL-4 production reflected a cell intrinsic role for PARP14 in Th2 cytokine control. Hence, our data suggest that although PARP14 has similar effects on T-cell cytokine production in several allergic disease models, the outcome of those effects is distinct, depending on the target organ of disease.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationKrishnamurthy, P., Da-Silva-Arnold, S., Turner, M. J., Travers, J. B. and Kaplan, M. H. (), PARP14 limits severity of allergic skin disease. Immunology. Accepted Author Manuscript. doi:10.1111/imm.12782en_US
dc.identifier.urihttps://hdl.handle.net/1805/13797
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.isversionof10.1111/imm.12782en_US
dc.relation.journalImmunologyen_US
dc.rightsPublisher Policyen_US
dc.sourceAuthoren_US
dc.subjectskin inflammationen_US
dc.subjectPARP14en_US
dc.subjectallergic skin diseaseen_US
dc.titlePoly-ADP ribose polymerase-14 limits severity of allergic skin diseaseen_US
dc.typeArticleen_US
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