Augmented Th17 differentiation in Trim21 deficiency promotes a stable phenotype of atherosclerotic plaques with high collagen content

Abstract

In this study, we demonstrate that TRIM21 influences atherosclerosis via regulation of Th17 responses, with TRIM21 deficiency promoting IL-17 expression and a more fibrous, stable, phenotype of the plaques.

COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options

“…83 In COVID-19 patients, medium-to long-term CV consequences may be caused by increased IL-6 signalling. Experimental evidence supports an atherogenic role for IL-6 and CRS-related cytokines, 59,60,[84][85][86] as well as its effects on cardiac fibrosis and failure. 87 The cytokine increases adhesion molecule expression in human endothelial cells in vitro; 88 at the same time, stimulation of human macrophages with oxidized LDLs (oxLDLs) leads to increased release of IL-6.…”

The Sjögren's syndrome-associated autoantigen Ro52/TRIM21 modulates follicular B cell homeostasis and immunoglobulin production

“…Interestingly, sterol metabolism has been observed to influence both immunoglobulin production and lymphocyte proliferation [47][48][49]. In addition, we have recently described an enhanced susceptibility to high-fat diet in Trim21 -/bone marrow-transferred Ldlr -/mice [19], with these mice developing significantly larger atherosclerotic plaques. This phenotype was linked to an increased differentiation and activation of the Th17 pathway in Trim21 -/mice, further emphasizing the link between altered sterol metabolism, the immune system and TRIM21.…”

“…We and others have previously observed that naive, unmanipulated Trim21-deficient mice display no obvious phenotype. More recently, Trim21-deficient naive T cells have also been shown to have an augmented intrinsic capacity for T helper type 17 (Th17) differentiation [19]. More recently, Trim21-deficient naive T cells have also been shown to have an augmented intrinsic capacity for T helper type 17 (Th17) differentiation [19].…”

“…However, upon chronic injury they develop severe tissue inflammation that progresses into systemic autoimmunity with hypergammaglobulinaemia and autoantibody production, revealing the importance of TRIM21 as a negative regulator of inflammatory responses [18]. More recently, Trim21-deficient naive T cells have also been shown to have an augmented intrinsic capacity for T helper type 17 (Th17) differentiation [19]. The B cell phenotype and the mechanisms by which TRIM21-deficiency leads to enhanced B cell activation and antibody production are, however, not well characterized.…”

The Active Compounds of Yixin Ningshen Tablet and Their Potential Action Mechanism in Treating Coronary Heart Disease‐ A Network Pharmacology and Proteomics Approach

“…us, we infer that Yixin Ningshen tablet may treat CHD primarily by regulating above 18 pathways, which awaits further validation. Of note, pathways with less than 10 target proteins, such as 17 cell differentiation (9) [95], VEGF signaling pathway (9) [96], Wnt signaling pathway (8) [97], folate biosynthesis (7) [98], tryptophan metabolism (6) [99], adipocytokine signaling pathway (6) [100], toll-like receptor signaling pathway (6) [101], choline metabolism (6) [102], platelet activation (5) [103], and linoleic acid metabolism (3) [104] were also validated to be closely related with CHD, which further proved the reliability of our target identification methods. e active compounds in Yixin Ningshen tablet regulate and restore the network equilibrium by targeting many proteins in many pathways, thereby mitigating the development of CHD.…”