| First Author | Lech M | Year | 2007 |
| Journal | Kidney Int | Volume | 72 |
| Issue | 2 | Pages | 182-92 |
| PubMed ID | 17495864 | Mgi Jnum | J:152887 |
| Mgi Id | MGI:4360176 | Doi | 10.1038/sj.ki.5002293 |
| Citation | Lech M, et al. (2007) Different roles of TiR8/Sigirr on toll-like receptor signaling in intrarenal antigen-presenting cells and tubular epithelial cells. Kidney Int 72(2):182-92 |
| abstractText | Toll-like receptors (TLRs) exist on both myeloid and intrinsic renal cells contributing to the initiation of innate immunity during renal infection with uropathogenic Escherichia coli. Toll-interleukin 1 receptor (IL-1R) (TIR)8/SIGIRR is an orphan receptor of the TLR/IL-1R family, which suppresses TLR signaling of immune cells and is highly expressed in the kidney. Lack of TIR8/SIGIRR is associated with enhanced renal chemokine signaling upon exposure to lipopolysaccharide (LPS). This was because of TIR8/SIGIRR expression on resident intrarenal myeloid cells rather than tubular epithelial cells which express it on basolateral and luminal membranes. The lack of TIR8/SIGIRR does not enhance TLR/IL-1R signaling in tubular epithelial cells as was observed in monocytes. TIR8/SIGIRR is induced in monocytes treated with LPS or tumor necrosis factor and interferon-gamma in a dose-dependent manner but was downregulated in treated tubule epithelial cells. This cell type-specific regulation and function did not relate to mRNA splice variants but was associated with N- and O-glycosylation of the receptor in renal cells of myeloid and nonmyeloid origin. Our studies show that resident myeloid cells contribute to TLR-mediated antimicrobial immunity in the kidney and that this function is controlled by Tir8/sigirr. TIR8/SIGIRR does not suppress TLR signaling in tubular epithelial cells, which supports their role as sensors of microbial infection in the kidney. |
