Toll-like receptor 9-induced type I IFN protects mice from experimental colitis Journal Article
| Authors: | Katakura, K.; Lee, J.; Rachmilewitz, D.; Li, G.; Eckmann, L.; Raz, E. |
| Article Title: | Toll-like receptor 9-induced type I IFN protects mice from experimental colitis |
| Abstract: | Experimental colitis is mediated by inflammatory or dysregulated immune responses to microbial factors of the gastrointestinal tract. In this study we observed that administration of Toll-like receptor 9 (TLR9) agonists suppressed the severity of experimental colitis in RAG1 -/- but not in SCID mice. This differential responsiveness between phenotypically similar but genetically distinct animals was related to a partial blockade in TLR9 signaling and defective production of type I IFN (i.e., IFN-α/β) in SCID mice upon TLR9 stimulation. The addition of neutralization antibodies against type IIFN abolished the antiinflammatory effects induced by TLR9 agonists, whereas the administration of recombinant IFN-β mimicked the antiinflammatory effects induced by TLR9 agonists in this model. Furthermore, mice deficient in the IFN-α/β receptor exhibited more severe colitis than wild-type mice did upon induction of experimental colitis. These results indicate that TLR9-triggered type I IFN has antiinflammatory functions in colitis. They also underscore the important protective role of type I IFN in intestinal homeostasis and suggest that strategies to modulate innate immunity may be of therapeutic value for the treatment of intestinal inflammatory conditions. |
| Keywords: | signal transduction; dna-binding proteins; interferon; nonhuman; alpha interferon; mouse; animals; mice; mice, knockout; cells, cultured; membrane proteins; homeodomain proteins; mice, scid; wild type; nuclear proteins; mice, inbred strains; cytokines; immune response; protein-serine-threonine kinases; histochemistry; adaptor proteins, signal transducing; colitis; enteritis; cytokine production; disease models, animal; homeostasis; beta interferon; colon; antibody; myeloid differentiation factor 88; receptor, interferon alpha-beta; antigens, differentiation; interferon-alpha; receptors, immunologic; receptors, cell surface; indicators and reagents; toll-like receptor 9; toll like receptor 9; culture media, conditioned; interferon-beta; dna-activated protein kinase; protection; dextran sulfate; experiment; receptors, interferon |
| Journal Title: | Journal of Clinical Investigation |
| Volume: | 115 |
| Issue: | 3 |
| ISSN: | 0021-9738 |
| Publisher: | American Society for Clinical Investigation |
| Date Published: | 2005-03-01 |
| Start Page: | 695 |
| End Page: | 702 |
| Language: | English |
| DOI: | 10.1172/jci200522996 |
| PUBMED: | 15765149 |
| PROVIDER: | scopus |
| PMCID: | PMC1051992 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 163" - "Export Date: 24 October 2012" - "CODEN: JCINA" - "Source: Scopus" |
