Lymphotoxin-beta receptor activation on macrophages ameliorates acute DSS-induced intestinal inflammation in a TRIM30伪-dependent manner

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• 作者：Nadin Wimmer^a ; Barbara Huber^a ; Anja K. Wege^a ; Nicola Barabas^a ; Johann Rö ; hrl^a ; Klaus Pfeffer^b ; Thomas Hehlgans^a ; ^{thomas.hehlgans@klinik.uni-regensburg.de}
• 关键词：LT尾R activation ; Conditional LT尾R-deficient mice ; TRIM30伪 ; DSS-induced intestinal inflammation
• 刊名：Molecular Immunology
• 出版年：2012
• 期刊代码：112_01615890
• 类别：bio
• 出版时间：June, 2012
• 卷：51
• 期：2
• 页码：128-135
• 文件大小：892 K

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.