Other
16 Authors
- Fairchild RL,
- Tuohy VK,
- de la Motte C,
- Vallance BA,
- Cua D,
- Kish D,
- Xiao H,
- Ma C,
- Wald D,
- Qin J,
- Li X,
- Gulen MF,
- Altuntas CZ,
- Bulek K,
- Zhou H,
- Yao J
| First Author | Xiao H | Year | 2007 |
| Journal | Immunity | Volume | 26 |
| Issue | 4 | Pages | 461-75 |
| PubMed ID | 17398123 | Mgi Jnum | J:123585 |
| Mgi Id | MGI:3718853 | Doi | 10.1016/j.immuni.2007.02.012 |
| Citation | Xiao H, et al. (2007) The Toll-interleukin-1 receptor member SIGIRR regulates colonic epithelial homeostasis, inflammation, and tumorigenesis. Immunity 26(4):461-75 |
| abstractText | Despite constant contact with the large population of commensal bacteria, the colonic mucosa is normally hyporesponsive to these potentially proinflammatory signals. Here we report that the single immunoglobulin IL-1 receptor-related molecule (SIGIRR), a negative regulator for Toll-IL-1R signaling, plays a critical role in gut homeostasis, intestinal inflammation, and colitis-associated tumorigenesis by maintaining the microbial tolerance of the colonic epithelium. SIGIRR-deficient (Sigirr(-/-)) colonic epithelial cells displayed commensal bacteria-dependent homeostatic defects, as shown by constitutive upregulation of inflammatory genes, increased inflammatory responses to dextran sulfate sodium (DSS) challenge, and increased Azoxymethane (AOM)+DSS-induced colitis-associated tumorigenesis. Gut epithelium-specific expression of the SIGIRR transgene in the SIGIRR-deficient background reduced the cell survival of the SIGIRR-deficient colon epithelium, abrogated the hypersensitivity of the Sigirr(-/-) mice to DSS-induced colitis, and reduced AOM+DSS-induced tumorigenesis. Taken together, our results indicate that epithelium-derived SIGIRR is critical in controlling the homeostasis and innate immune responses of the colon to enteric microflora. |
