IL-22 affects smooth muscle cell phenotype and plaque formation in apolipoprotein E knockout mice

Rattik, Sara; Hultman, Karin; Rauch, Uwe; Söderberg, Ingrid; Sundius, Lena; Ljungcrantz, Irena; Hultgårdh‐Nilsson, Anna; Wigren, Maria; Björkbacka, Harry; Fredrikson, Gunilla Nordin; Nilsson, Jan

doi:10.1016/j.atherosclerosis.2015.08.006

Cited by 42 publications

(42 citation statements)

References 43 publications

(41 reference statements)

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“…Mice treated with the anti–IL‐22 neutralizing mAb exhibited the opposite results. These findings suggest that IL‐22 affects the dedifferentiation of SMCs, a conclusion that is consistent with the research of Sara Rattik, who observed decreased expression of genes associated with contraction after stimulating SMCs with IL‐22 in vitro …”

Section: Discussionsupporting

confidence: 91%

IL‐22 produced by Th22 cells aggravates atherosclerosis development in ApoE^−/− mice by enhancing DC‐induced Th17 cell proliferation

Shi

Liu

et al. 2020

J Cellular Molecular Medi

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Th22 cells are a novel subset of CD4+ T cells that primarily mediate biological effects through IL‐22, with both Th22 cells and IL‐22 being closely associated with multiple autoimmune and chronic inflammatory diseases. In this study, we investigated whether and how Th22 cells affect atherosclerosis. ApoE−/− mice and age‐matched C57BL/6J mice were fed a Western diet for 0, 4, 8 or 12 weeks. The results of dynamic analyses showed that Th22 cells, which secrete the majority of IL‐22 among the known CD4+ cells, play a major role in atherosclerosis. ApoE−/− mice fed a Western diet for 12 weeks and administered recombinant mouse IL‐22 (rIL‐22) developed substantially larger plaques in both the aorta and aortic root and higher levels of CD3+ T cells, CD68+ macrophages, collagen, IL‐6, Th17 cells, dendritic cells (DCs) and pSTAT3 but lower smooth muscle cell (SMC) α‐actin expression than the control mice. Treatment with a neutralizing anti–IL‐22 monoclonal antibody (IL‐22 mAb) reversed the above effects. Bone marrow‐derived DCs exhibited increased differentiation into mature DCs following rIL‐22 and ox‐LDL stimulation. IL‐17 and pSTAT3 were up‐regulated after stimulation with IL‐22 and ox‐LDL in cells cocultured with CD4+ T cells and mature DC supernatant, but this up‐regulation was significantly inhibited by IL‐6mAb or the cell‐permeable STAT3 inhibitor S31‐201. Thus, Th22 cell‐derived IL‐22 aggravates atherosclerosis development through a mechanism that is associated with IL‐6/STAT3 activation, DC‐induced Th17 cell proliferation and IL‐22–stimulated SMC dedifferentiation into a synthetic phenotype.

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Section: Discussionsupporting

confidence: 91%

IL‐22 produced by Th22 cells aggravates atherosclerosis development in ApoE^−/− mice by enhancing DC‐induced Th17 cell proliferation

Shi

Liu

et al. 2020

J Cellular Molecular Medi

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“…It was suggested that IL-22 activates migration of SMCs from the aortic media to the intima, and therefore promotes plaque development [57]. We found that IL-22 presumably acts as an antiatherogenic molecule, possibly, due to its capability to regulate barrier function and microbial activity in the intestine.…”

Section: Role Of Cytokines In the Development Of Atherosclerosismentioning

confidence: 62%

The role of cytokines in the development of atherosclerosis

Fatkhullina

Peshkova

Koltsova

2016

Biochemistry Moscow

225

159

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Atherosclerosis contributes to the development of many cardiovascular diseases, which remain the leading cause of death in developed countries. Atherosclerosis is a chronic inflammatory disease of large and medium-sized arteries. It is caused by dyslipidemia and mediated by both innate and adaptive immune responses. Inflammation is a key factor at all stages of atherosclerosis progression. Cells involved in pathogenesis of atherosclerosis were shown to be activated by soluble factors, cytokines that strongly influence the disease development. Pro-inflammatory cytokines accelerate atherosclerosis progression, while anti-inflammatory cytokines ameliorate the disease. In this review, we discuss the latest findings on the role of cytokines in the development and progression of atherosclerosis.

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“…In the case of atherosclerosis, IL-22 −/− Apoe −/− mice exhibited reduced plaque size and decreased plaque collagen level, which are important in the maintenance of plaque stability. IL-22 might promote plaque growth and contribute to plaque stability during lesion formation [27]. …”

Section: Discussionmentioning

confidence: 99%

Interleukin-22 Might Act as a Double-Edged Sword in Type 2 Diabetes and Coronary Artery Disease

Gong

Zhou

et al. 2016

Mediators of Inflammation

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Type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) are both characterized by chronic low-grade inflammation. The role of Th17 and its related cytokines in T2DM and CAD is unclear. Here we investigated the serum levels of five Th17-related cytokines (IL-17, IL-22, MIP-3α, IL-9, and IL-27) in T2DM, CAD, and T2DM-CAD comorbidity patients. IL-22 was found to be elevated in all three conditions. Elevated serum IL-22 was independently associated with the incidence of T2DM and CAD. Conversely, IL-22 was found to protect endothelial cells from glucose- and lysophosphatidylcholine- (LPC-) induced injury, and IL-22R1 expression on endothelial cells was increased upon treatment with high glucose and LPC. Blocking of IL-22R1 with IL-22R1 antibody diminished the protective role of IL-22. Our results suggest that IL-22 functions as a double-edged sword in T2DM and CAD and that IL-22 may be used in the treatment of chronic inflammatory diseases such as T2DM and CAD.

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IL-22 affects smooth muscle cell phenotype and plaque formation in apolipoprotein E knockout mice

Cited by 42 publications

References 43 publications

IL‐22 produced by Th22 cells aggravates atherosclerosis development in ApoE^−/− mice by enhancing DC‐induced Th17 cell proliferation

IL‐22 produced by Th22 cells aggravates atherosclerosis development in ApoE^−/− mice by enhancing DC‐induced Th17 cell proliferation

The role of cytokines in the development of atherosclerosis

Interleukin-22 Might Act as a Double-Edged Sword in Type 2 Diabetes and Coronary Artery Disease

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IL-22 affects smooth muscle cell phenotype and plaque formation in apolipoprotein E knockout mice

Cited by 42 publications

References 43 publications

IL‐22 produced by Th22 cells aggravates atherosclerosis development in ApoE−/− mice by enhancing DC‐induced Th17 cell proliferation

IL‐22 produced by Th22 cells aggravates atherosclerosis development in ApoE−/− mice by enhancing DC‐induced Th17 cell proliferation

The role of cytokines in the development of atherosclerosis

Interleukin-22 Might Act as a Double-Edged Sword in Type 2 Diabetes and Coronary Artery Disease

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Product

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IL‐22 produced by Th22 cells aggravates atherosclerosis development in ApoE^−/− mice by enhancing DC‐induced Th17 cell proliferation

IL‐22 produced by Th22 cells aggravates atherosclerosis development in ApoE^−/− mice by enhancing DC‐induced Th17 cell proliferation