Dendritic Cells and Regulatory T Cells in Atherosclerosis

Cheong, Cheolho; Choi, Jae‐Hoon

doi:10.1007/s10059-012-0128-9

Cited by 23 publications

(14 citation statements)

References 60 publications

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“…Mouse spleen and lymph nodes (LNs) were digested in 400 U/ml of collagenase D (Roche) in RPMI 1640 for 30 min at 37˚C. Foxp3 + T cells were stained using a Foxp3 staining buffer set (eBioscience) according to a previously described method (31); all other intracellular stainings were performed using a Fixation/Permeabilization Solution Kit (BD Biosciences). Stained cells were acquired or sorted using an LSRFortessa flow cytometer or FACSAria III (BD Biociences), respectively, and analyzed with FlowJo (Treestar).…”

Section: Heart Single-cell Isolation and Flow Cytometrymentioning

confidence: 99%

Conventional Dendritic Cells Impair Recovery after Myocardial Infarction

Lee

Jeong

Kim

et al. 2018

The Journal of Immunology

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Ischemic myocardial injury results in sterile cardiac inflammation that leads to tissue repair, two processes controlled by mononuclear phagocytes. Despite global burden of cardiovascular diseases, we do not understand the functional contribution to pathogenesis of specific cardiac mononuclear phagocyte lineages, in particular dendritic cells. To address this limitation, we used detailed lineage tracing and genetic studies to identify bona fide murine and human CD103 conventional dendritic cell (cDC)1s, CD11b cDC2s, and plasmacytoid DCs (pDCs) in the heart of normal mice and immunocompromised NSG mice reconstituted with human CD34 cells, respectively. After myocardial infarction (MI), the specific depletion of cDCs, but not pDCs, improved cardiac function and prevented adverse cardiac remodeling. Our results showed that fractional shortening measured after MI was not influenced by the absence of pDCs. Interestingly, however, depletion of cDCs significantly improved reduction in fractional shortening. Moreover, fibrosis and cell areas were reduced in infarcted zones. This correlated with reduced numbers of cardiac macrophages, neutrophils, and T cells, indicating a blunted inflammatory response. Accordingly, mRNA levels of proinflammatory cytokines IL-1β and IFN-γ were reduced. Collectively, our results demonstrate the unequivocal pathological role of cDCs following MI.

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Section: Heart Single-cell Isolation and Flow Cytometrymentioning

confidence: 99%

Conventional Dendritic Cells Impair Recovery after Myocardial Infarction

Lee

Jeong

Kim

et al. 2018

The Journal of Immunology

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“…Thus, future work is warranted to elucidate the functional mechanisms that regulate T reg cells during atherosclerosis in vivo. Furthermore, it will be interesting to examine the effects of CD137 on immune‐boosting DCs, which were recently shown to be involved in the initiation and progression of atherosclerosis (16, 48), and to play an important role in maintaining T reg cells (49, 50).…”

Section: Discussionmentioning

confidence: 99%

CD137‐inducing factors from T cells and macrophages accelerate the destabilization of atherosclerotic plaques in hyperlipidemic mice

et al. 2014

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CD137 (4-1BB), a member of the tumor necrosis factor receptor superfamily, has been reported to be expressed in atherosclerotic plaques, and to promote lesion formation. However, the role of CD137 in mediating atherosclerotic plaque stability and the possible underlying molecular and cellular mechanisms are poorly understood. Here, apolipoprotein E-deficient (ApoE(-/-)) and CD137-deficient ApoE(-/-) (ApoE(-/-)CD137(-/-)) mice fed a chow diet for 66 wk were used. CD137 induces plaque instability, which is characterized by increased plaque necrosis, decreased collagen content, decreased vascular smooth muscle cell (VSMC) content, and increased macrophage infiltration. CD137 also increases the infiltration of effector T (Teff) cells into plaque lesion sites, resulting in increased interferon-γ (IFN-γ) expression. Interestingly, Teff-cell-derived IFN-γ inhibits collagen synthesis in atherosclerotic plaques. Furthermore, CD137 activation increases the apoptosis of VSMCs, possibly by decreasing the antiapoptotic regulator, Bcl-2, and subsequently up-regulating cleaved caspase-3. In macrophages, activation of CD137 signaling boosted the oxidized low density lipoprotein-induced expression of matrix metalloproteinase 9 via the p38 mitogen-activated protein kinase and extracellular signal-regulated kinase1/2 signaling pathways. In summary, activation of CD137 signaling decreases the stability of advanced atherosclerotic plaques via its combined effects on Teff cells, VSMCs, and macrophages.

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“…Dendritic cells are professional antigen-presenting cells that are pivotal in regulating immune responses, particularly T-cell stimulation [59]. Moreover, DCs have been implicated in vascular pathologies including aortic aneurysm and atherosclerosis [22,60,61]. For instance, activated DCs have been shown to accumulate in atherosclerotic lesions in the aortic intima at the onset and throughout development of this disease whereas, in contrast, in the absence of disease, the resident DCs found in the intima of normal human aortae display an immature phenotype [62,63].…”

Section: Discussionmentioning

confidence: 99%

“…Chemokine receptors mediate the migration of DCs to secondary lymphoid tissues where they initiate adaptive immune responses [21]. Notably, functional DCs have been found residing in both human and mouse blood vessels [22,23]. Moreover, several studies have strongly implicated DC involvement in vascular pathology.…”

Section: Introductionmentioning

confidence: 99%

The effect of cyclic mechanical strain on activation of dendritic cells cultured on adhesive substrates

et al. 2013

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Dendritic cells (DCs), key regulators of tolerance and immunity, have been found to reside in mechanically active tissues such as the interior layers of the arterial wall, which experience cyclic radial wall strain due to pulsatile blood flow. Although experimentally difficult to determine in vivo, it is reasonable to postulate DCs experience the mechanical forces in such mechanically active tissues. However, it is currently unknown how DCs respond to cyclic mechanical strain. In order to explore the hypothesis that DCs are responsive to mechanical strain, DCs were cultured in vitro on pre-adsorbed adhesive proteins (e.g., laminin, collagen, fibrinogen) and 1 Hz cyclic strain was applied for various durations and strain magnitudes. It was determined that a strain magnitude of 10% and 24 h duration adversely affected DC viability compared to no-strain controls, but culture on certain adhesive substrates provided modest protection of viability under this harsh strain regime. In contrast, application of 1 h of 1 Hz cyclic 3% strain did not affect DC viability and this strain regime was used for the remaining experiments for quantifying DC activation and T-cell priming capability. Application of 3% strain increased expression of stimulatory (MHC-II) and co-stimulatory molecules (CD86, CD40), and this effect was generally increased by culture on pre-coated adhesive substrates. Interestingly, the cytokine secretion profile of DCs was not significantly affected by strain. Lastly, strained DCs demonstrated increased stimulation of allogeneic T cell proliferation, in a manner that was independent of the adhesive substrate. These observations indicate generation of a DC consistent with what has been described as a semi-mature phenotype. This work begins elucidating a potential role for DCs in tissue environments exposed to cyclic mechanical forces.

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Dendritic Cells and Regulatory T Cells in Atherosclerosis

Cited by 23 publications

References 60 publications

Conventional Dendritic Cells Impair Recovery after Myocardial Infarction

Conventional Dendritic Cells Impair Recovery after Myocardial Infarction

CD137‐inducing factors from T cells and macrophages accelerate the destabilization of atherosclerotic plaques in hyperlipidemic mice

The effect of cyclic mechanical strain on activation of dendritic cells cultured on adhesive substrates

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