Lymphotoxin-beta receptor activation on macrophages ameliorates acute DSS-induced intestinal inflammation in a TRIM30α-dependent manner
| Autor: | Johann Röhrl, Thomas Hehlgans, Barbara Huber, Nadin Wimmer, Klaus Pfeffer, Anja K. Wege, Nicola Barabas |
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| Rok vydání: | 2012 |
| Předmět: |
CD4-Positive T-Lymphocytes
Adoptive cell transfer Dependent manner T cell Immunology Cell Enzyme-Linked Immunosorbent Assay Biology Real-Time Polymerase Chain Reaction Negative regulator Mice Lymphotoxin beta Receptor Intestinal inflammation medicine Animals Molecular Biology Mice Knockout Reverse Transcriptase Polymerase Chain Reaction Macrophages Dextran Sulfate Intracellular Signaling Peptides and Proteins Colitis Coculture Techniques Cell biology Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Female Signal transduction Lymphotoxin beta receptor |
| Zdroj: | Molecular Immunology. 51:128-135 |
| ISSN: | 0161-5890 |
| DOI: | 10.1016/j.molimm.2012.02.118 |
| Popis: | Our previous studies indicated that LTβR activation mainly by T cell derived LTα1β2 is crucial for the control and down-regulation of intestinal inflammation. In order to dissect the cellular and molecular role of LTβR activation in the experimental model of DSS-induced intestinal inflammation, we have generated cell type-specific LTβR-deficient mice with specific ablation of LTβR expression on macrophages/neutrophils (LTβR(flox/flox) × LysM-Cre). These mice develop an exacerbated intestinal inflammation in our experimental model indicating that LTβR 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 LTβR-deficient mice. Furthermore, transfer of activated CD4+ T cells derived from wild-type mice, but not from LTβR ligand-deficient mice attenuated the signs of intestinal inflammation. Finally, we demonstrate that LTβR activation on BMDM results in induction of TRIM30α, a negative regulator of NFκB activation. Concordantly, ablation of LTβR signaling results in the inability to induce TRIM30α expression concomitant with an increased expression of pro-inflammatory cytokines in our experimental model. Taken together, our data demonstrate that LTβR activation on macrophages by CD4+ T cell derived LTαβ controls the pro-inflammatory response by activation of a TRIM30α-dependent signaling pathway, crucial for the down-regulation of the inflammatory response in this experimental model. |
| Databáze: | OpenAIRE |
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