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.

Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE

Publication: Bethesda, MD : American Association of Immunologists
Original Publication: Baltimore : Williams & Wilkins, c1950-

Cytokines/*metabolism ; Interleukin-10/*metabolism ; Killer Cells, Natural/*metabolism ; Macrophages/*metabolism ; Receptor, Interferon alpha-beta/*metabolism ; STAT Transcription Factors/*metabolism; Animals ; Immunity, Innate/physiology ; Interleukins/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Signal Transduction/physiology

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.
(Copyright © 2018 by The American Association of Immunologists, Inc.)

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R01 AI070594 United States AI NIAID NIH HHS; R01 AI113910 United States AI NIAID NIH HHS

0 (Cytokines)
0 (IL10 protein, mouse)
0 (Il24 protein, mouse)
0 (Interleukins)
0 (STAT Transcription Factors)
0 (interleukin-24)
130068-27-8 (Interleukin-10)
156986-95-7 (Receptor, Interferon alpha-beta)

Date Created: 20180214 Date Completed: 20190219 Latest Revision: 20241102

20241102

PMC5840025

10.4049/jimmunol.1701340

29436412