| First Author | Su X | Year | 2014 |
| Journal | J Leukoc Biol | Volume | 96 |
| Issue | 1 | Pages | 17-26 |
| PubMed ID | 24550525 | Mgi Jnum | J:212032 |
| Mgi Id | MGI:5577226 | Doi | 10.1189/jlb.0813457 |
| Citation | Su X, et al. (2014) Epigenetically modulated LRRC33 acts as a negative physiological regulator for multiple Toll-like receptors. J Leukoc Biol 96(1):17-26 |
| abstractText | The members of a LRR family play crucial roles in the activation of innate and adaptive immune responses. We reported previously that LRRC33, a transmembrane protein of the LRR family, might potentially affect TLR-mediated activity. Here, we demonstrate that LRRC33 is a negative physiological regulator for multiple TLRs. Lrrc33(-/-) and Lrrc33(+/-) mice were more susceptible to TLR ligand challenges. The macrophages and DCs from Lrrc33(-/-) mice produced more proinflammatory cytokines than those of WT mice through increased activation of MAPK and NF-kappaB. Silencing LRRC33 also promoted multiple TLR-mediated activation in human moDCs. Notably, LRRC33 expression could be down-regulated by TLR ligands LPS, poly I:C, or PGN through H3K4me3 and H3K27me3 modification. In LPS-conditioned moDCs, reduced enrichment of H3K4me3 and increased H3K27me3 could be observed at the promoter region of LRRC33. Furthermore, silencing H3K4me3-associated factors MLL and RBBP5 not only decreased the enrichment of H3K4me3 but also down-regulated expression of LRRC33, whereas the expression of LRRC33 was up-regulated after silencing H3K27me3-associated factors EZH2 and EED. Thus, our results suggest that LRRC33 and TLRs may form a negative-feedback loop, which is important for the maintenance of immune homeostasis. |
