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The RNA uridyltransferase Zcchc6 is expressed in macrophages and impacts innate immune responses.

TitleThe RNA uridyltransferase Zcchc6 is expressed in macrophages and impacts innate immune responses.
Publication TypeJournal Article
Year of Publication2017
AuthorsKozlowski E, Wasserman GA, Morgan M, O'Carroll D, Ramirez N-GP, Gummuluru S, Rah JY, Gower AC, Ieong M, Quinton LJ, Mizgerd JP, Jones MR
JournalPLoS One
Volume12
Issue6
Paginatione0179797
Date Published2017
ISSN1932-6203
Abstract

Alveolar macrophages orchestrate pulmonary innate immunity and are essential for early immune surveillance and clearance of microorganisms in the airways. Inflammatory signaling must be sufficiently robust to promote host defense but limited enough to prevent excessive tissue injury. Macrophages in the lungs utilize multiple transcriptional and post-transcriptional mechanisms of inflammatory gene expression to delicately balance the elaboration of immune mediators. RNA terminal uridyltransferases (TUTs), including the closely homologous family members Zcchc6 (TUT7) and Zcchc11 (TUT4), have been implicated in the post-transcriptional regulation of inflammation from studies conducted in vitro. In vivo, we observed that Zcchc6 is expressed in mouse and human primary macrophages. Zcchc6-deficient mice are viable and born in Mendelian ratios and do not exhibit an observable spontaneous phenotype under basal conditions. Following an intratracheal challenge with S. pneumoniae, Zcchc6 deficiency led to a modest but significant increase in the expression of select cytokines including IL-6, CXCL1, and CXCL5. These findings were recapitulated in vitro whereby Zcchc6-deficient macrophages exhibited similar increases in cytokine expression due to bacterial stimulation. Although loss of Zcchc6 also led to increased neutrophil emigration to the airways during pneumonia, these responses were not sufficient to impact host defense against infection.

DOI10.1371/journal.pone.0179797
Alternate JournalPLoS ONE
PubMed ID28665939
Publication institute
CRM