Lymphotoxin-beta receptor signalling regulates cytokine expression via TRIM30α in a TRAF3-dependent manner

Wimmer, Nadin; Heigl, Ulrike; Klingseisen, Laura; Schneider-Brachert, Wulf; Hehlgans, Thomas

doi:10.1016/j.molimm.2012.10.036

Cited by 9 publications

(6 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…26 In contrast, other studies have found that LTbR signaling by macrophages during acute colitis induced by dextran sodium sulfate exerts protective, anti-inflammatory functions by activating the tripartite motif containing 30α signaling pathway. 27 Therefore, the immunomodulatory functions of LTbR seem to be context-specific. One interesting aspect of the phenotype of apoE …”

Section: Discussionmentioning

confidence: 99%

Deficiency in Lymphotoxin β Receptor Protects From Atherosclerosis in apoE-Deficient Mice

Grandoch

Feldmann

Göthert

et al. 2015

Circulation Research

View full text Add to dashboard Cite

Rationale: Lymphotoxin β receptor (LTbR) regulates immune cell trafficking and communication in inflammatory diseases. However, the role of LTbR in atherosclerosis is still unclear. Objective: The aim of this study was to elucidate the role of LTbR in atherosclerosis. Methods and Results: After 15 weeks of feeding a Western-type diet, mice double-deficient in apolipoprotein E and LTbR (apoE −/− /LTbR −/− ) exhibited lower aortic plaque burden than did apoE −/− littermates. Macrophage content at the aortic root and in the aorta was reduced, as determined by immunohistochemistry and flow cytometry. In line with a decrease in plaque inflammation, chemokine (C–C motif) ligand 5 ( Ccl5 ) and other chemokines were transcriptionally downregulated in aortic tissue from apoE −/− /LTbR −/− mice. Moreover, bone marrow chimeras demonstrated that LTbR deficiency in hematopoietic cells mediated the atheroprotection. Furthermore, during atheroprogression, apoE −/− mice exhibited increased concentrations of cytokines, for example, Ccl5, whereas apoE −/− /LTbR −/− mice did not. Despite this decreased plaque macrophage content, flow cytometric analysis showed that the numbers of circulating lymphocyte antigen 6C (Ly6C) low monocytes were markedly elevated in apoE −/− /LTbR −/− mice. The influx of these cells into atherosclerotic lesions was significantly reduced, whereas apoptosis and macrophage proliferation in atherosclerotic lesions were unaffected. Gene array analysis pointed to chemokine (C–C motif) receptor 5 as the most regulated pathway in isolated CD115 + cells in apoE −/− /LTbR −/− mice. Furthermore, stimulating monocytes from apoE −/− mice with agonistic anti-LTbR antibody or the natural ligand lymphotoxin-α1β2, increased Ccl5 mRNA expression. Conclusions: These findings suggest that LTbR plays a role in macrophage-driven inflammation in atherosclerotic lesions, probably by augmenting the Ccl5-mediated recruitment of monocytes.

show abstract

Section: Discussionmentioning

confidence: 99%

Deficiency in Lymphotoxin β Receptor Protects From Atherosclerosis in apoE-Deficient Mice

Grandoch

Feldmann

Göthert

et al. 2015

Circulation Research

View full text Add to dashboard Cite

show abstract

“…TRIM30 is the mouse homolog of human TRIM5α protein, which exerts an anti-retroviral function in various cell types; however, to date, the role of TRIM30 in mice has been linked only with innate immune responses in macrophages and dendritic cells [15], [16], [20]. In this report, we established TRIM30 as a key regulator of TCR-induced signaling in CD4 + T cells.…”

Section: Discussionmentioning

confidence: 73%

Tripartite Motif-Containing Protein 30 Modulates TCR-Activated Proliferation and Effector Functions in CD4+ T Cells

et al. 2014

View full text Add to dashboard Cite

To avoid excessive activation, immune signals are tightly controlled by diverse inhibitory proteins. TRIM30, a tripartite motif (TRIM)-containing protein is one of such inhibitors known to function in macrophages. To define the roles of TRIM30, we generated Trim30 knockout (Trim30 −/−) mice. Trim30 deletion caused no major developmental defects in any organs, nor showed any discernable defect in the activation of macrophages. But, Trim30 −/− mice showed increased CD4/CD8 ratio when aged and Trim30 −/− CD4+ T cells exhibited an abnormal response upon TCR activation, in particular in the absence of a costimulatory signal. Adoptive transfer of wild-type and Trim30 −/− CD4+ T cells together into lymphopenic hosts confirmed higher proliferation of the Trim30 −/− CD4+ T cells in vivo. Despite the enhanced proliferation, Trim30 −/− T cells showed decreased levels of NF-κB activation and IL-2 production compared to wild-type cells. These results indicate a distinct requirement for TRIM30 in modulation of NF-κB activation and cell proliferation induced by TCR stimulation.

show abstract

“…TRIM30a is of mouse origin and is a homologue of human TRIM5a. To date, TRIM30 has primarily been linked to innate immune responses in macrophages and dendritic cells [23,33,34]. TRIM30a has also been linked to the regulation of numerous other cellular processes, such as differentiation, development, proliferation, apoptosis, antiviral responses and oncogenesis [23].…”

Section: Discussionmentioning

confidence: 99%

Suppression of protein quality control system by TRIM30a sensitises tumour cells to NK cell‐mediated immune surveillance

Afolabi,

Bi,

Chen

et al. 2023

Immunology

View full text Add to dashboard Cite

Tumorigenesis entails circumventing cell‐intrinsic regulatory mechanisms while avoiding extrinsic immune surveillance and other host defence systems. Nevertheless, how tumour cells' ability to eliminate misfolded proteins affects immune surveillance remains poorly understood. In this study, we find that overexpression of murine tripartite motif‐containing protein 30a (TRIM30a) sensitises tumour cells to natural killer (NK) cells‐mediated cytolysis. TRIM30a has no effect on tumour cell proliferation or apoptosis in vitro. However, TRIM30a‐overexpressing tumour cells grow substantially slower than control tumour cells in immune‐competent mice but not in NK cell‐depleted mice. [Correction added on 04 October 2023, after first online publication: ‘NK‐depleted’ has been changed to ‘NK cell‐depleted’ in the preceding sentence.] Mechanistically, TRIM30a overexpression impedes the clearance of misfolded proteins and increases the production of reactive oxygen species induced by proteotoxic stress, implying that TRIM30a impairs protein quality control (PQC) systems in tumour cells. Furthermore, TRIM30a reduces expression of genes encoding proteasome subunits and antioxidant proteins. Our study demonstrates that TRIM30a is a potential tumour suppressor and immune modulator that promotes tumour cytolysis by NK cells, and suggests that an enhanced PQC and antioxidant capacity is an integral part of the immune escape mechanism during tumorigenesis.

show abstract

Lymphotoxin-beta receptor signalling regulates cytokine expression via TRIM30α in a TRAF3-dependent manner

Cited by 9 publications

References 28 publications

Deficiency in Lymphotoxin β Receptor Protects From Atherosclerosis in apoE-Deficient Mice

Deficiency in Lymphotoxin β Receptor Protects From Atherosclerosis in apoE-Deficient Mice

Tripartite Motif-Containing Protein 30 Modulates TCR-Activated Proliferation and Effector Functions in CD4+ T Cells

Suppression of protein quality control system by TRIM30a sensitises tumour cells to NK cell‐mediated immune surveillance

Contact Info

Product

Resources

About