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Updated: May 23, 2026
Investigating Intestinal Inflammation in DSS-induced Model of IBD
Published on: February 1, 2012
Lymphotoxin-beta receptor activation on macrophages ameliorates acute DSS-induced intestinal inflammation in a
Nadin Wimmer1, Barbara Huber, Anja K Wege
1Institute of Immunology, University of Regensburg, 93053 Regensburg, Germany.
Abstract:
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.
Insights
LTβR activation on macrophages is crucial for controlling intestinal inflammation. This pathway, involving TRIM30α, down-regulates inflammatory responses, as shown in DSS-induced models.
Area of Science:
- Immunology
- Gastroenterology
- Molecular Biology
Background:
- LTβR activation is vital for controlling intestinal inflammation.
- Previous studies highlighted T cell-derived LTα₁β₂ as a key activator.
Purpose of the Study:
- To investigate the specific role of LTβR activation on macrophages and neutrophils in DSS-induced intestinal inflammation.
- To elucidate the cellular and molecular mechanisms underlying LTβR-mediated control of inflammation.
Main Methods:
- Generation of cell type-specific LTβR-deficient mice (LTβR((flox/flox))×LysM-Cre).
- Adoptive transfer experiments using bone marrow-derived macrophages (BMDM) and CD4+ T cells.
- Analysis of TRIM30α and NFκB signaling pathways, and pro-inflammatory cytokine expression.
Main Results:
- LTβR deficiency in macrophages/neutrophils exacerbated DSS-induced intestinal inflammation.
- LTβR activation on BMDM induced TRIM30α, a negative regulator of NFκB.
- Ablation of LTβR signaling impaired TRIM30α induction and increased pro-inflammatory cytokines.
Conclusions:
- LTβR signaling on macrophages, activated by CD4+ T cell-derived LTαβ, controls intestinal inflammation.
- This control is mediated by the TRIM30α-dependent pathway, which down-regulates NFκB activation and pro-inflammatory responses.
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