Cell-specific requirements for STAT proteins and Type i IFN receptor signaling discretely regulate IL-24 and IL-10 expression in NK cells and macrophages

Djeneba Dabitao, Christian M. Hedrich, Fengying Wang, Vimvara Vacharathit, Jay Bream

Research output: Contribution to journalArticle

Abstract

Il10 forms a cytokine cluster with Il19, Il20, and Il24 in a conserved region of chromosome 1. The latter genes are in the IL-20 subfamily of IL-10-related cytokines and, although they are not as well studied their biologic actions and expression patterns, seem to have little in common with IL-10. IL-24, like IL-10, however, is uniquely expressed in T cells and is a signature gene of the Th2 lineage, which suggests they could be coregulated in certain cell types. Little is known about other cellular sources of IL-24. We investigated IL-24 and IL-10 expression in murine macrophages and NK cells, and found that although they are coexpressed under most stimulation conditions, IL-24 and IL-10 are controlled by distinct, cell type-specific pathways. In bone marrow-derived macrophages, optimal IL-24 expression required LPS+IL-4 costimulation and STAT6 but was independent of type I IFN receptor signaling and STAT4. Conversely, LPS-induced IL-10 was independent of IL-4/STAT6 and STAT4 but, consistent with other reports, required type I IFN receptor signaling for optimal expression. Remarkably, NK-specific IL-24 (but not IL-10) expression was dependent on both type I IFN receptor signaling and STAT4. Induction of IL-24 expression was accompanied by cell-specific recruitment of STAT6 and STAT4 to multiple sites that we identified within Il24, which mediated STAT-dependent histone modifications across the gene. Collectively, our results indicate that despite being coexpressed, IL-10 and IL-24 are independently regulated by different type I IFN receptor signaling pathways in innate immune cells and provide insight into the mechanisms that fine-tune cell type-specific gene expression within the Il10 cluster.

Original languageEnglish (US)
Pages (from-to)2154-2164
Number of pages11
JournalJournal of Immunology
Volume200
Issue number6
DOIs
StatePublished - Mar 15 2018

ASJC Scopus subject areas

  • Immunology

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