摘要
Our previous studies indicated that LT尾R activation mainly by T cell derived LT伪1尾2 is crucial for the control and down-regulation of intestinal inflammation. In order to dissect the cellular and molecular role of LT尾R activation in the experimental model of DSS-induced intestinal inflammation, we have generated cell type-specific LT尾R-deficient mice with specific ablation of LT尾R expression on macrophages/neutrophils (LT尾R(flox/flox) 脳 LysM-Cre). These mice develop an exacerbated intestinal inflammation in our experimental model indicating that LT尾R 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 LT尾R-deficient mice. Furthermore, transfer of activated CD4+ T cells derived from wild-type mice, but not from LT尾R ligand-deficient mice attenuated the signs of intestinal inflammation. Finally, we demonstrate that LT尾R activation on BMDM results in induction of TRIM30伪, a negative regulator of NF魏B activation. Concordantly, ablation of LT尾R signaling results in the inability to induce TRIM30伪 expression concomitant with an increased expression of pro-inflammatory cytokines in our experimental model. Taken together, our data demonstrate that LT尾R activation on macrophages by CD4+ T cell derived LT伪尾 controls the pro-inflammatory response by activation of a TRIM30伪-dependent signaling pathway, crucial for the down-regulation of the inflammatory response in this experimental model.