Wimmer, Nadin and Huber, Barbara and Wege, Anja K. and Barabas, Nicola and Roehrl, Johann and Pfeffer, Klaus and Hehlgans, Thomas (2012) Lymphotoxin-beta receptor activation on macrophages ameliorates acute DSS-induced intestinal inflammation in a TRIM30 alpha-dependent manner. MOLECULAR IMMUNOLOGY, 51 (2). pp. 128-135. ISSN 0161-5890,
Full text not available from this repository. (Request a copy)Abstract
Our previous studies indicated that LT beta R activation mainly by T cell derived LT alpha(1)beta(2) is crucial for the control and down-regulation of intestinal inflammation. In order to dissect the cellular and molecular role of LT beta R activation in the experimental model of DSS-induced intestinal inflammation, we have generated cell type-specific LT beta R-deficient mice with specific ablation of LT beta R expression on macrophages/neutrophils (LT beta R-(flox/flox) x LysM-Cre). These mice develop an exacerbated intestinal inflammation in our experimental model indicating that LT beta 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 beta R-deficient mice. Furthermore, transfer of activated CD4(+) T cells derived from wild-type mice, but not from LT beta R ligand-deficient mice attenuated the signs of intestinal inflammation. Finally, we demonstrate that LT beta R activation on BMDM results in induction of TRIM30 alpha, a negative regulator of NF kappa B activation. Concordantly, ablation of LT beta R signaling results in the inability to induce TRIM30 alpha expression concomitant with an increased expression of pro-inflammatory cytokines in our experimental model. Taken together, our data demonstrate that LT beta R activation on macrophages by CD4(+) T cell derived LT alpha beta controls the pro-inflammatory response by activation of a TRIM30 alpha-dependent signaling pathway, crucial for the down-regulation of the inflammatory response in this experimental model. (c) 2012 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EXPERIMENTAL COLITIS; LYMPHOID-TISSUES; EXPRESSION; CELLS; LIGHT; TNF; LT beta R activation; Conditional LT beta R-deficient mice; TRIM30 alpha; DSS-induced intestinal inflammation |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 May 2020 05:38 |
| Last Modified: | 13 May 2020 05:38 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18657 |
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