CD4+LAP+ and CD4+CD25+Foxp3+ Regulatory T Cells Induced by Nasal Oxidized Low-Density Lipoprotein Suppress Effector T Cells Response and Attenuate Atherosclerosis in ApoE−/− Mice

Zhong, Yucheng; Wang, Xiang; Ji, Qingwei; Mao, Xiaobo; Tang, Hongxia; Gao, Yi; Meng, Kai; Yang, Xiaofang; Zeng, Qiutang

doi:10.1007/s10875-012-9699-7

Cited by 43 publications

(52 citation statements)

References 40 publications

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“…In preclinical models, nasal or oral administration of HSP65 reduced atherosclerosis in Ldlr -/-mice (146,147). Similar findings are reported for nasal administration of oxLDL (148,149) or β2-glycoprotein I (150). Another approach is to deliver the relevant antigens via tolerogenic DCs that have suppressed costimulatory functions but maintain antigen-presenting functions.…”

Section: Regulation Of Proatherogenic Adaptive Immune Responsessupporting

confidence: 59%

Adaptive immunity in atherogenesis: new insights and therapeutic approaches

Lichtman¹,

Binder²,

Tsimikas³

et al. 2013

J. Clin. Invest.

176

171

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Many remarkable advances have improved our understanding of the cellular and molecular events in the pathogenesis of atherosclerosis. Chief among these is the accumulating knowledge of how the immune system contributes to all phases of atherogenesis, including well-known inflammatory reactions consequent to intimal trapping and oxidation of LDL. Advances in our understanding of the innate and adaptive responses to these events have helped to clarify the role of inflammation in atherogenesis and suggested new diagnostic modalities and novel therapeutic targets. Here we focus on recent advances in understanding how adaptive immunity affects atherogenesis.

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Section: Regulation Of Proatherogenic Adaptive Immune Responsessupporting

confidence: 59%

Adaptive immunity in atherogenesis: new insights and therapeutic approaches

Lichtman¹,

Binder²,

Tsimikas³

et al. 2013

J. Clin. Invest.

176

171

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“…Both IL-10 and TGF-β1 have been confirmed to exhibit antiatherogenic properties using different approaches including transfer gene models, knockout models, neutralization, and adenovirus expression vector 2, 3, 9 . In our previous studies, we also found that TGF-β plays a vital role in an oxLDL and thymic stromal lymphopoietin (TSLP) treated atherosclerosis prone model 25, 26, 35 . Because not blocking TGF-β1 signaling but blocking IL-10 signaling significantly abolished the protective effects of IL-37 in a myocardial I/R injury model 12 , and because the ascending range of IL-10 was more significant than TGF-β1 in the present study, the anti-IL-10R mAb was used to clarify whether IL-10 is indispensable for the protective role of IL-37 in atherosclerosis.…”

Section: Discussionmentioning

confidence: 88%

Exogenous interleukin 37 ameliorates atherosclerosis via inducing the Treg response in ApoE-deficient mice

Meng

et al. 2017

Sci Rep

Self Cite

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Our previous study indicated that interleukin (IL)-37 is involved in atherosclerosis. In the present study, Anterior tibial arteries were collected from diabetes patients and controls. A histopathological analysis showed that IL-37 was over-expressed in human atherosclerotic plaques. Many types of cells including macrophages, vascular smooth muscle cells (VSMCs), endothelial cells and T lymphocyte expressed IL-37 in human atherosclerotic plaques. ApoE−/− mice were divided into a control group and a recombinant human IL-37-treated group. The IL-37 treatment resulted in a significant decrease in macrophages and CD4+ T lymphocytes and a substantial increase in VSMCs and collagen in atherosclerotic plaques, resulting in a reduction in atherosclerotic plaque size. Furthermore, the IL-37 treatment modulated the CD4+ T lymphocyte activity, including a decrease in T helper cell type 1 (Th1) and Th17 cells and an increase in regulatory T (Treg) cells, and inhibited the maturity of dendritic cells both in vivo and in vitro. In addition, treatment with anti-IL-10 receptor monoclonal antibody abrogated the anti-atherosclerotic effects of IL-37. These data suggest that exogenous IL-37 ameliorates atherosclerosis via inducing the Treg response. IL-37 may be a novel therapeutic to prevent and treat atherosclerotic disease.Atherosclerosis is a chronic inflammatory disease in the arterial wall that is initiated mainly in response to oxidized lipoproteins and controlled by immune system 1-3 . Both innate immunity, which is antigen-and memory-independent, and adaptive immunity, which is antigen-and memory-dependent, are involved in atherosclerosis 2 . The main cell type involved in innate immunity is macrophage. In contrast, T cells and dendritic cells (DCs) are the main cell types in adaptive immunity. Regulating the immune response has been considered as the therapeutic target for the treatment of atherosclerosis 4, 5 .The novel anti-inflammatory cytokine interleukin (IL)-37 is a new member of the IL-1 family, and is only interleukin of this family that is absent in mice 6, 7 . The IL-1 family consists of 11 members, including IL-1α, IL-1β, IL-1Rα, IL-18, IL-33, IL-36Rα, IL-36α, IL-36β, IL-36γ, IL-37 and IL-38 8 . Most of the cytokines of the IL-1 family, such as IL-1 and IL-18, are pro-inflammatory cytokines and significantly promote the development of atherosclerosis 9 . Some, such as IL-1Rα and IL-33, are anti-inflammatory cytokines and efficiently ameliorate atherosclerosis in mice whereas the function of IL-36α remains unclear 9 . Evidence shows that both exogenous

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“…Once an antigen reaches the cervical lymph nodes, however, it is likely that immune responses to CNS antigens may be constrained by the same mechanisms associated with mucosal tolerance induction, including TGFβ production by T regulatory cells (Treg; ref. 28), production of antibodies that signal through inhibitory Fc receptors like CD32 (FcRIIB; ref. 29), and preferential presentation in germinal centers, resulting in skewing toward B-cell predominant responses (30).…”

Section: Redefining Cns Immune Privilegementioning

confidence: 99%

Immunotherapy for Brain Cancer: Recent Progress and Future Promise

Jackson¹,

Lim²,

Drake

2014

Clinical Cancer Research

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Immunotherapy is emerging as the newest pillar of cancer treatment, with the potential to assume a place alongside surgical debulking, radiotherapy, and chemotherapy. Early experiences with antitumor vaccines demonstrated the feasibility and potential efficacy of this approach, and newer agents, such as immune checkpoint blocking antibodies and modern vaccine platforms, have ushered in a new era. These efforts are headlined by work in melanoma, prostate cancer, and renal cell carcinoma; however, substantial progress has been achieved in a variety of other cancers, including high-grade gliomas. A recurrent theme of this work is that immunotherapy is not a one-size-fits-all solution. Rather, dynamic, tumor-specific interactions within the tumor microenvironment continually shape the immunologic balance between tumor elimination and escape. High-grade gliomas are a particularly fascinating example. These aggressive, universally fatal tumors are highly resistant to radiotherapy and chemotherapy and inevitably recur after surgical resection. Located in the immune-privileged central nervous system, high-grade gliomas also use an array of defenses that serve as direct impediments to immune attack. Despite these challenges, vaccines have shown activity against high-grade gliomas, and anecdotal, preclinical, and early clinical data bolster the notion that durable remission is possible with immunotherapy. Realizing this potential, however, will require an approach tailored to the unique aspects of glioma biology.

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CD4+LAP+ and CD4+CD25+Foxp3+ Regulatory T Cells Induced by Nasal Oxidized Low-Density Lipoprotein Suppress Effector T Cells Response and Attenuate Atherosclerosis in ApoE−/− Mice

Cited by 43 publications

References 40 publications

Adaptive immunity in atherogenesis: new insights and therapeutic approaches

Adaptive immunity in atherogenesis: new insights and therapeutic approaches

Exogenous interleukin 37 ameliorates atherosclerosis via inducing the Treg response in ApoE-deficient mice

Immunotherapy for Brain Cancer: Recent Progress and Future Promise

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