Canonical wnt signaling in CD11c + APCs regulates microbiota-Induced inflammation and immune cell homeostasis in the colon

Daniel Swafford, Arul Kumaran Shanmugam, Punithavathi Ranganathan, Mohamed S. Hussein, Pandelakis Koni, Puttur D Prasad, Muthusamy Thangaraju, Santhakumar Manicassamy

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Aberrant Wnt/b-catenin signaling occurs in several inflammatory diseases, including inflammatory bowel disease and inflammatory bowel disease–associated colon carcinogenesis. However, its role in shaping mucosal immune responses to commensals in the gut remains unknown. In this study, we investigated the importance of canonical Wnt signaling in CD11c + APCs in controlling intestinal inflammation. Using a mouse model of ulcerative colitis, we demonstrated that canonical Wnt signaling in intestinal CD11c + APCs controls intestinal inflammation by imparting an anti-inflammatory phenotype. Genetic deletion of Wnt coreceptors, low-density lipoprotein receptor–related proteins 5 and 6 (LRP5/6) in CD11c + APCs in LRP5/6 DCD11c mice, resulted in enhanced intestinal inflammation with increased histopathological severity of colonic tissue. This was due to microbiota-dependent increased production of proinflammatory cytokines and decreased expression of immune-regulatory factors such as IL-10, retinoic acid, and IDO. Mechanistically, loss of LRP5/6-mediated signaling in CD11c + APCs resulted in altered microflora and T cell homeostasis. Furthermore, our study demonstrates that conditional activation of b-catenin in CD11c + APCs in LRP5/6 D CD11c mice resulted in reduced intestinal inflammation with decreased histopathological severity of colonic tissue. These results reveal a mechanism by which intestinal APCs control intestinal inflammation and immune homeostasis via the canonical Wnt-signaling pathway. The Journal of Immunology, 2018, 200: 3259–3268.

Original languageEnglish (US)
Pages (from-to)3259-3268
Number of pages10
JournalJournal of Immunology
Volume200
Issue number9
DOIs
StatePublished - May 1 2018

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Microbiota
Colon
Homeostasis
Inflammation
Lipoproteins
Catenins
Wnt Signaling Pathway
Proteins
Mucosal Immunity
Immunologic Factors
Tretinoin
Allergy and Immunology
LDL Lipoproteins
Ulcerative Colitis
Inflammatory Bowel Diseases
Interleukin-10
Carcinogenesis
Anti-Inflammatory Agents
Cytokines
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Canonical wnt signaling in CD11c + APCs regulates microbiota-Induced inflammation and immune cell homeostasis in the colon . / Swafford, Daniel; Shanmugam, Arul Kumaran; Ranganathan, Punithavathi; Hussein, Mohamed S.; Koni, Pandelakis; Prasad, Puttur D; Thangaraju, Muthusamy; Manicassamy, Santhakumar.

In: Journal of Immunology, Vol. 200, No. 9, 01.05.2018, p. 3259-3268.

Research output: Contribution to journalArticle

Swafford, Daniel ; Shanmugam, Arul Kumaran ; Ranganathan, Punithavathi ; Hussein, Mohamed S. ; Koni, Pandelakis ; Prasad, Puttur D ; Thangaraju, Muthusamy ; Manicassamy, Santhakumar. / Canonical wnt signaling in CD11c + APCs regulates microbiota-Induced inflammation and immune cell homeostasis in the colon In: Journal of Immunology. 2018 ; Vol. 200, No. 9. pp. 3259-3268.
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