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Th17 cells and IL-17 are involved in the disruption of vulnerable plaques triggered by short-term combination stimulation in apolipoprotein E-knockout mice.

ABSTRACT: Considerable evidence indicates that type 1 T helper (Th1)- and Th17-mediated immune responses promote the formation of atherosclerotic plaques while that CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) have a protective effect. However, the functions of diverse CD4(+) lymphocyte subsets in plaque rupture remain poorly understood because of a shortage of satisfactory plaque rupture models. Here, we established a murine model of atherosclerotic plaque rupture using a high-fat diet and collar placement on the carotid artery, and triggered plaque rupture by short-term stimulation with a combination of lipopolysaccharide, phenylephrine injection and cold in apolipoprotein E-knockout (ApoE(-/-)) mice. We investigated the associations between Th1 cells, Th17 cells and Tregs and plaque rupture by PCR, flow cytometry, ELISA and immunohistochemistry. In total, 75% (18/24) of vulnerable plaques, but no stable plaques, showed rupture characteristics. The proportion of Th17 cells was increased among splenocytes after treatment, but the changes in the levels of Th1 cells and Tregs were not related to rupture. Furthermore, the treatment resulted in high levels of interleukin-17 (IL-17) in the serum and in the region of plaque rupture. In vitro, IL-17 increased the level of apoptosis, a major factor associated with plaque rupture, in cultured murine vascular smooth muscle cells. Th17 cells and IL-17 may be involved in the disruption of vulnerable plaques triggered by short-term stimulation with lipopolysaccharide, phenylephrine injection and cold in ApoE(-/-)mice.

SUBMITTER: Ma T

PROVIDER: S-EPMC4003212 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Th17 cells and IL-17 are involved in the disruption of vulnerable plaques triggered by short-term combination stimulation in apolipoprotein E-knockout mice.

Ma Tian T Gao Qi Q Zhu Faliang F Guo Chun C Wang Qun Q Gao Fei F Zhang Lining L

Cellular & molecular immunology 20130401 4

Considerable evidence indicates that type 1 T helper (Th1)- and Th17-mediated immune responses promote the formation of atherosclerotic plaques while that CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) have a protective effect. However, the functions of diverse CD4(+) lymphocyte subsets in plaque rupture remain poorly understood because of a shortage of satisfactory plaque rupture models. Here, we established a murine model of atherosclerotic plaque rupture using a high-fat diet and collar pla ...[more]

PMID: 23542316

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Project description:Systemic lupus erythematosus (SLE) is a disease characterized by dysregulation and hyperreactivity of the immune response at various levels, including hyperactivation of effector cell subtypes, autoantibodies production, immune complex formation, and deposition in tissues. The consequences of hyperreactivity to the self are systemic and local inflammation and tissue damage in multiple organs. Lupus nephritis (LN) is one of the most worrying manifestations of SLE, and most patients have this involvement at some point in the course of the disease. Among the effector cells involved, the Th17, a subtype of T helper cells (CD4+), has shown significant hyperactivation and participates in kidney damage and many other organs. Th17 cells have IL-17A and IL-17F as main cytokines with receptors expressed in most renal cells, being involved in the activation of many proinflammatory and profibrotic pathways. The Th17/IL-17 axis promotes and maintains repetitive tissue damage and maladaptive repair; leading to fibrosis, loss of organ architecture and function. In the podocytes, the Th17/IL-17 axis effects include changes of the cytoskeleton with increased motility, decreased expression of health proteins, increased oxidative stress, and activation of the inflammasome and caspases resulting in podocytes apoptosis. In renal tubular epithelial cells, the Th17/IL-17 axis promotes the activation of profibrotic pathways such as increased TGF-β expression and epithelial-mesenchymal transition (EMT) with consequent increase of extracellular matrix proteins. In addition, the IL-17 promotes a proinflammatory environment by stimulating the synthesis of inflammatory cytokines by intrinsic renal cells and immune cells, and the synthesis of growth factors and chemokines, which together result in granulopoiesis/myelopoiesis, and further recruitment of immune cells to the kidney. The purpose of this work is to present the prognostic and immunopathologic role of the Th17/IL-17 axis in Kidney diseases, with a special focus on LN, including its exploration as a potential immunotherapeutic target in this complication.

Dataset Information

Th17 cells and IL-17 are involved in the disruption of vulnerable plaques triggered by short-term combination stimulation in apolipoprotein E-knockout mice.

Publications

Th17 cells and IL-17 are involved in the disruption of vulnerable plaques triggered by short-term combination stimulation in apolipoprotein E-knockout mice.

Similar Datasets

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