| First Author | Wimmer N | Year | 2012 |
| Journal | Mol Immunol | Volume | 51 |
| Issue | 2 | Pages | 128-35 |
| PubMed ID | 22437076 | Mgi Jnum | J:184872 |
| Mgi Id | MGI:5426491 | Doi | 10.1016/j.molimm.2012.02.118 |
| Citation | Wimmer N, et al. (2012) Lymphotoxin-beta receptor activation on macrophages ameliorates acute DSS-induced intestinal inflammation in a TRIM30alpha-dependent manner. Mol Immunol 51(2):128-35 |
| abstractText | Our previous studies indicated that LTbetaR activation mainly by T cell derived LTalpha(1)beta(2) is crucial for the control and down-regulation of intestinal inflammation. In order to dissect the cellular and molecular role of LTbetaR activation in the experimental model of DSS-induced intestinal inflammation, we have generated cell type-specific LTbetaR-deficient mice with specific ablation of LTbetaR expression on macrophages/neutrophils (LTbetaR((flox/flox))xLysM-Cre). These mice develop an exacerbated intestinal inflammation in our experimental model indicating that LTbetaR expression on macrophages/neutrophils is responsible for the control and down-regulation of the inflammatory reaction. These results were verified by adoptive transfer experiments of BMDM from wild-type and LTbetaR-deficient mice. Furthermore, transfer of activated CD4+ T cells derived from wild-type mice, but not from LTbetaR ligand-deficient mice attenuated the signs of intestinal inflammation. Finally, we demonstrate that LTbetaR activation on BMDM results in induction of TRIM30alpha, a negative regulator of NFkappaB activation. Concordantly, ablation of LTbetaR signaling results in the inability to induce TRIM30alpha expression concomitant with an increased expression of pro-inflammatory cytokines in our experimental model. Taken together, our data demonstrate that LTbetaR activation on macrophages by CD4+ T cell derived LTalphabeta controls the pro-inflammatory response by activation of a TRIM30alpha-dependent signaling pathway, crucial for the down-regulation of the inflammatory response in this experimental model. |
