Chronic skin inflammation accelerates macrophage cholesterol crystal formation and atherosclerosis

Baumer, Yvonne; Ng, Qimin; Sanda, Gregory E.; Dey, Amit; Teague, Heather; Sorokin, Alexander V.; Dagur, Pradeep K.; Silverman, Joanna I; Harrington, Charlotte; Rodante, Justin; Rose, Shawn; Varghese, Nevin; Belur, Agastya D.; Goyal, Aditya; Gelfand, Joel M.; Springer, Danielle; Bleck, Christopher K. E.; Thomas, Charlotte L; Yu, Zu‐Xi; Winge, M; Kruth, Howard S.; Marinkovich, M. Peter; Joshi, Aditya; Playford, Martin P.; Mehta, Nehal N.

doi:10.1172/jci.insight.97179

Cited by 48 publications

(42 citation statements)

References 61 publications

(71 reference statements)

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“…In another set of experiments PBMCs were differentiated into macrophages based on the adhesion method as described previously and cultivated for 7 days in vitro in X-Vivo15 media supplemented with 20% FBS [30]. For each setup, cells were fixed using 2.5% glutaraldehyde (0.1 M calcium chloride, 0.1 M sodium cacodylate buffer, pH 7.2) for 1 h at RT and prepared as described previously [30][31][32][33] using polypropylene syringe filter holders (Cat: Pall Life science 4317, 13 mm Swinney, USA) with an inserted 0.1 μm disk filter (Pall Life Sciences, USA) and 1 ml insulin syringes (SS1D2516, Terumo, USA). Then samples were coated with 5 nm gold/ palladium using the EMS 575-X sputter coater (Electron Microscopy Sciences, Hatfield, USA).…”

Section: Scanning Electron Microscopy (Sem)mentioning

confidence: 99%

Immune cell phenotyping in low blood volumes for assessment of cardiovascular disease risk, development, and progression: a pilot study

et al. 2020

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Background: Cardiovascular disease (CVD) is the leading cause of death in the world. Given the role of immune cells in atherosclerosis development and progression, effective methods for characterizing immune cell populations are needed, particularly among populations disproportionately at risk for CVD. Results: By using a variety of antibodies combined in one staining protocol, we were able to identify granulocyte, lymphocyte, and monocyte sub-populations by CD-antigen expression from 500 µl of whole blood, enabling a more extensive comparison than what is possible with a complete blood count and differential (CBC). The flow cytometry panel was established and tested in a total of 29 healthy men and women. As a proof of principle, these 29 samples were split by their race/ethnicity: African-Americans (AA) (N = 14) and Caucasians (N = 15). We found in accordance with the literature that AA had fewer granulocytes and more lymphocytes when compared to Caucasians, though the proportion of total monocytes was similar in both groups. Several new differences between AA and Caucasians were noted that had not been previously described. For example, AA had a greater proportion of platelet adhesion on nonclassical monocytes when compared to Caucasians, a cell-to-cell interaction described as crucially important in CVD. We also examined our flow panel in a clinical population of AA women with known CVD risk factors (N = 20). Several of the flow cytometry parameters that cannot be measured with the CBC displayed correlations with clinical CVD risk markers. For instance, Framingham Risk Score (FRS) calculated for each participant correlated with immune cell platelet aggregates (PA) (e.g. T cell PA β = 0.59, p = 0.03 or non-classical monocyte PA β = 0.54, p = 0.02) after adjustment for body mass index (BMI). Conclusion: A flow cytometry panel identified differences in granulocytes, monocytes, and lymphocytes between AA and Caucasians which may contribute to increased CVD risk in AA. Moreover, this flow panel identifies immune

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Section: Scanning Electron Microscopy (Sem)mentioning

confidence: 99%

Immune cell phenotyping in low blood volumes for assessment of cardiovascular disease risk, development, and progression: a pilot study

et al. 2020

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“…While the traditional paradigm of T cell lineages might predominate shared mechanistic links between psoriasis and atherosclerosis, there is significant heterogeneity and plasticity within the T cell subtypes. T cell predominance may change in context of subtype preponderance with the natural disease course, specifically, a switch from Th1 dominated profile in early initiation phase of psoriasis to a Th17 governed response in the chronic inflammatory phase with both involved in atherosclerosis progression ( 99 ).…”

Section: Potential Immunologic Links Between Psoriasis and Cvdmentioning

confidence: 99%

“…While macrophages are traditionally subclassified as pro-inflammatory (M1) and anti-inflammatory (M2), they are known to be plastic and adapt to the surrounding milieu according to the underlying pathological state ( 103 , 104 ). Furthermore, a preclinical in vivo and in vitro study demonstrated that chronic skin inflammation in psoriasis polarizes them toward the pro-atherosclerotic phenotype ( 99 ). These cells are involved in ACS, and their increased expression and activity is also present in vulnerable plaques ( 105 ).…”

Section: Potential Immunologic Links Between Psoriasis and Cvdmentioning

confidence: 99%

Potential Immunological Links Between Psoriasis and Cardiovascular Disease

Sajja¹,

Joshi²,

Teague³

et al. 2018

Front. Immunol.

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Preclinical and clinical research provide strong evidence that chronic, systemic inflammation plays a key role in development and progression of atherosclerosis. Indeed, chronic inflammatory diseases, such as psoriasis, are associated with accelerated atherosclerosis and increased risk of cardiovascular events. Contemporary research has demonstrated plausible mechanistic links between immune cell dysfunction and cardiometabolic disease in psoriasis. In this review, we describe the role of potential common immunological mechanisms underlying both psoriasis and atherogenesis. We primarily discuss innate and adaptive immune cell subsets and their contributions to psoriatic disease and cardiovascular morbidity. Emerging efforts should focus on understanding the interplay among immune cells, adipose tissue, and various biomarkers of immune dysfunction to provide direction for future targeted therapy.

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“…18 Support for systemic feed-forward inflammation originated from studies in transgenic mice: misexpressing inflammatory products in KCs led to increases in vascular inflammation, arthritis, and soluble mediators in the circulation. 19,20 Cultured human skin models also support the model: a role for KC differentiation and connective tissue in the response to IL-17A is evidenced by the approximately 10 times increase in the number of IL-17A-induced genes in stratified human skin cultures compared with monolayer KC cultures, 21 in part because of higher levels of the transcription factors CCAAT enhancerbinding protein (C/EBP) b or C/EBPd, which mediate IL-17induced signals in differentiated spinous and granular KC layers. 13 Finally, synergistic activity of IL-17A with nuclear factor k-light-chain enhancer of activated B cells (NF-kB)-activating factors, such as TNF and IL-1, can occur through linked NF-kB and C/EBP binding sites in the promoters of many IL-17-responsive genes.…”

mentioning

confidence: 99%

IL-17A inhibition by secukinumab induces early clinical, histopathologic, and molecular resolution of psoriasis

Krueger

Wharton

Schlitt

et al. 2019

Journal of Allergy and Clinical Immunology

137

106

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and East Hanover, NJ GRAPHICAL ABSTRACT Background: Hyperactivity of the IL-23/IL-17 axis is central to plaque psoriasis pathogenesis. Secukinumab, a fully human mAb that selectively inhibits IL-17A, is approved for treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis. Secukinumab improves the complete spectrum of psoriasis manifestations, with durable clinical responses beyond 5 years From a the

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Chronic skin inflammation accelerates macrophage cholesterol crystal formation and atherosclerosis

Cited by 48 publications

References 61 publications

Immune cell phenotyping in low blood volumes for assessment of cardiovascular disease risk, development, and progression: a pilot study

Immune cell phenotyping in low blood volumes for assessment of cardiovascular disease risk, development, and progression: a pilot study

Potential Immunological Links Between Psoriasis and Cardiovascular Disease

IL-17A inhibition by secukinumab induces early clinical, histopathologic, and molecular resolution of psoriasis

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