| First Author | Katakura K | Year | 2005 |
| Journal | J Clin Invest | Volume | 115 |
| Issue | 3 | Pages | 695-702 |
| PubMed ID | 15765149 | Mgi Jnum | J:110027 |
| Mgi Id | MGI:3630245 | Doi | 10.1172/JCI22996 |
| Citation | Katakura K, et al. (2005) Toll-like receptor 9-induced type I IFN protects mice from experimental colitis. J Clin Invest 115(3):695-702 |
| abstractText | 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-alpha/beta) in SCID mice upon TLR9 stimulation. The addition of neutralization antibodies against type I IFN abolished the antiinflammatory effects induced by TLR9 agonists, whereas the administration of recombinant IFN-beta mimicked the antiinflammatory effects induced by TLR9 agonists in this model. Furthermore, mice deficient in the IFN-alpha/beta 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. |
