2011 journal article

Antigen-Presenting Cell Production of IL-10 Inhibits T-Helper 1 and 17 Cell Responses and Suppresses Colitis in Mice

GASTROENTEROLOGY, 141(2), 653–U764.

By: B. Liu, S. Tonkonogy n & R. Sartor *

author keywords: Mouse Model; Inflammatory Bowel Disease; Immune Response; Microbiota
MeSH headings : Adaptive Immunity; Animals; Antigen-Presenting Cells / drug effects; Antigen-Presenting Cells / metabolism; Antigens, Bacterial / immunology; CD11b Antigen / metabolism; CD4-Positive T-Lymphocytes / metabolism; Cells, Cultured; Colitis / immunology; DNA-Binding Proteins / deficiency; DNA-Binding Proteins / genetics; Forkhead Transcription Factors / metabolism; Germ-Free Life; Immunity, Innate; Interferon-gamma / metabolism; Interleukin-10 / deficiency; Interleukin-10 / genetics; Interleukin-10 / immunology; Interleukin-10 / metabolism; Interleukin-10 / pharmacology; Interleukin-12 / metabolism; Interleukin-17 / metabolism; Mice; Mice, Knockout; RNA, Messenger / metabolism; Signal Transduction; Smad Proteins; T-Box Domain Proteins / metabolism; T-Lymphocytes, Regulatory / cytology; Th1 Cells / immunology; Th17 Cells / immunology; Transforming Growth Factor beta / metabolism; Tretinoin / physiology
TL;DR: IL-10 produced by APCs regulates homeostatic T-cell responses to commensal bacteria and induced more severe colitis and higher levels of inflammatory cytokines in IL-10(-/-), Rag2-replete, Rag2(-/-) mice. (via Semantic Scholar)
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Source: Web Of Science
Added: August 6, 2018

BACKGROUND & AIMS Mice that are deficient in interleukin (IL)-10 develop colitis, mediated by T-helper (Th)1 and Th17 cells, and IL-10-producing regulatory T (Treg) cells suppress colitis, implicating IL-10 in maintaining mucosal homeostasis. We assessed the relative importance of immunoregulatory IL-10 derived from T cells or from antigen presenting cells (APCs) in development of intestinal inflammation. METHODS CD4(+) cells from germ-free (GF) or specific pathogen-free (SPF) IL-10(-/-) or wild-type mice were injected into IL-10(-/-), Rag2(-/-) mice or Rag2(-/-) mice that express IL-10. After 6-8 weeks, we evaluated inflammation, spontaneous secretion of cytokines from colonic tissue, and mRNA levels of the transcription factor T-bet and the immunoregulatory cytokine transforming growth factor (TGF)-β. CD4(+) T cells were co-cultured with bacterial lysate-pulsed APCs and assayed for cytokine production, FoxP3 expression, and TGF-β-mediated Smad signaling. RESULTS CD4(+) cells from GF or SPF IL-10(-/-) or wild-type mice induced more severe colitis and higher levels of inflammatory cytokines in IL-10(-/-), Rag2(-/-) mice than in IL-10-replete, Rag2(-/-) mice. Co-cultures of IL-10(-/-) or wild-type CD4(+) T cells plus bacterial lysate-pulsed APCs from IL-10(-/-) mice contained more interferon (IFN)-γ, IL-12/23p40, and IL-17 than co-cultures of the same T cells plus APCs from wild-type mice. CD11b(+) APCs were required for these effects. Blocking IL-10 receptors increased production of IFN-γ and IL-12/23p40 whereas exogenous IL-10 suppressed these cytokines. IL-10-producing APCs induced TGF-β-mediated, retinoic acid-dependent, differentiation of FoxP3(+) Treg cells, whereas blocking the retinoic acid receptor, in vitro and in vivo, reduced proportions of FoxP3(+) Treg cells. CONCLUSIONS IL-10 produced by APCs regulates homeostatic T-cell responses to commensal bacteria.