STING-Dependent Signaling Underlies IL-10 Controlled Inflammatory Colitis

Jeonghyun Ahn, Sehee Son, Sergio C. Oliveira, Glen N Barber

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Intestinal immune homeostasis is preserved by commensal bacteria interacting with the host to generate a balanced array of cytokines that are essential for wound repair and for combatting infection. Inflammatory bowel disease (IBD), which can lead to colitis-associated cancer (CAC), is thought to involve chronic microbial irritation following a breach of the mucosal intestinal epithelium. However, the innate immune pathways responsible for regulating these inflammatory processes remain to be fully clarified. Here, we show that commensal bacteria influence STING signaling predominantly in mononuclear phagocytes to produce both pro-inflammatory cytokines as well as anti-inflammatory IL-10. Enterocolitis, manifested through loss of IL-10, was completely abrogated in the absence of STING. Intestinal inflammation was less severe in the absence of cGAS, possibly suggesting a role for cyclic dinucleotides (CDNs) indirectly regulating STING signaling. Our data shed insight into the causes of inflammation and provide a potential therapeutic target for prevention of IBD. Ahn et al. find a key role for STING signaling in controlling gut homeostasis. Loss of STING reverses colitis observed in the absence of the anti-inflammatory cytokine IL-10 in mice. The interface of commensal bacteria with mononuclear phagocytes (MNPs) containing STING is responsible for stimulating pro- as well as anti-inflammatory cytokine expression.

Original languageEnglish (US)
Pages (from-to)3873-3884
Number of pages12
JournalCell Reports
Volume21
Issue number13
DOIs
StatePublished - Dec 26 2017

Fingerprint

Colitis
Interleukin-10
Cytokines
Bacteria
Anti-Inflammatory Agents
Phagocytes
Inflammatory Bowel Diseases
Homeostasis
Inflammation
Enterocolitis
Intestinal Mucosa
Repair
Wounds and Injuries
Infection
Neoplasms
Therapeutics

Keywords

  • CAC
  • colitis-associated cancer
  • IBD
  • IL-10
  • inflammatory bowel disease
  • STING

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

STING-Dependent Signaling Underlies IL-10 Controlled Inflammatory Colitis. / Ahn, Jeonghyun; Son, Sehee; Oliveira, Sergio C.; Barber, Glen N.

In: Cell Reports, Vol. 21, No. 13, 26.12.2017, p. 3873-3884.

Research output: Contribution to journalArticle

Ahn, Jeonghyun ; Son, Sehee ; Oliveira, Sergio C. ; Barber, Glen N. / STING-Dependent Signaling Underlies IL-10 Controlled Inflammatory Colitis. In: Cell Reports. 2017 ; Vol. 21, No. 13. pp. 3873-3884.
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