High-density lipoprotein immunomodulates the functional activities of macrophage and cytokines produced during ex vivo macrophage-CD4 + T cell crosstalk at the recent-onset human type 1 diabetes

Benghalem, Ibtissem; Warda, Meziane; Hadjidj, Zeyneb; Ysmail-Dahlouk, Lamia; Belamri, Ahmed; Mouhadjer, Kheira; Aribi, Mourad

doi:10.1016/j.cyto.2017.03.001

Cited by 10 publications

(3 citation statements)

References 89 publications

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“…HDL stimulates the release of cytokines, including IL-10 [287]. In turn, IL-10 itself affects lipid metabolism, which leads to severe dyslipidemia, low HDL-C, low LDL-C, and elevated triglyceride levels [288].…”

Section: Tumor-induced Metabolic Changes Interfere With the Profile Omentioning

confidence: 99%

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

2020

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Background Tumor initiation and subsequent progression are usually long-term processes, spread over time and conditioned by diverse aspects. Many cancers develop on the basis of chronic inflammation; however, despite dozens of years of research, little is known about the factors triggering neoplastic transformation under these conditions. Molecular characterization of both pathogenetic states, i.e., similarities and differences between chronic inflammation and cancer, is also poorly defined. The secretory activity of tumor cells may change the immunophenotype of immune cells and modify the extracellular microenvironment, which allows the bypass of host defense mechanisms and seems to have diagnostic and prognostic value. The phenomenon of immunosuppression is also present during chronic inflammation, and the development of cancer, due to its duration, predisposes patients to the promotion of chronic inflammation. The aim of our work was to discuss the above issues based on the latest scientific insights. A theoretical mechanism of cancer immunosuppression is also proposed. Conclusions Development of solid tumors may occur both during acute and chronic phases of inflammation. Differences in the regulation of immune responses between precancerous states and the cancers resulting from them emphasize the importance of immunosuppressive factors in oncogenesis. Cancer cells may, through their secretory activity and extracellular transport mechanisms, enhance deterioration of the immune system which, in turn, may have prognostic implications.

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Section: Tumor-induced Metabolic Changes Interfere With the Profile Omentioning

confidence: 99%

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

2020

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“…Defective uptake of lipoproteins coincided with a diminished iNKT cell IL-4 response in previous mouse studies 22 , suggesting that lipoproteins can enhance iNKT cell IL-4 production. Moreover, co-culture studies of macrophages and CD4 + T cells showed that supplementation of HDL-cholesterol induced the IL-4 production of CD4 + T cells 23 . Potential mechanisms involved still require further elucidation.…”

Section: Discussionmentioning

confidence: 99%

Immunometabolic factors in adolescent chronic disease are associated with Th1 skewing of invariant Natural Killer T cells

Ververs

Engelen

Nuboer

et al. 2021

Sci Rep

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Invariant Natural Killer T (iNKT) cells respond to the ligation of lipid antigen-CD1d complexes via their T-cell receptor and are implicated in various immunometabolic diseases. We considered that immunometabolic factors might affect iNKT cell function. To this end, we investigated iNKT cell phenotype and function in a cohort of adolescents with chronic disease and immunometabolic abnormalities. We analyzed peripheral blood iNKT cells of adolescents with cystic fibrosis (CF, n = 24), corrected coarctation of the aorta (CoA, n = 25), juvenile idiopathic arthritis (JIA, n = 20), obesity (OB, n = 20), and corrected atrial septal defect (ASD, n = 25) as controls. To study transcriptional differences, we performed RNA sequencing on a subset of obese patients and controls. Finally, we performed standardized co-culture experiments using patient plasma, to investigate the effect of plasma factors on iNKT cell function. We found comparable iNKT cell numbers across patient groups, except for reduced iNKT cell numbers in JIA patients. Upon ex-vivo activation, we observed enhanced IFN-γ/IL-4 cytokine ratios in iNKT cells of obese adolescents versus controls. The Th1-skewed iNKT cell cytokine profile of obese adolescents was not explained by a distinct transcriptional profile of the iNKT cells. Co-culture experiments with patient plasma revealed that across all patient groups, obesity-associated plasma factors including LDL-cholesterol, leptin, and fatty-acid binding protein 4 (FABP4) coincided with higher IFN-γ production, whereas high HDL-cholesterol and insulin sensitivity (QUICKI) coincided with higher IL-4 production. LDL and HDL supplementation in co-culture studies confirmed the effects of lipoproteins on iNKT cell cytokine production. These results suggest that circulating immunometabolic factors such as lipoproteins may be involved in Th1 skewing of the iNKT cell cytokine response in immunometabolic disease.

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“…In addition, IL-2, a cytokine essential for the proliferation and differentiation of CD8 + T cells, may invalidate the inhibition mediated by PD-1. Conversely, PD-1 may indirectly inhibit T cell function and survival through IL-2 (Francisco et al, 2010), while HDL can reduce IL-2 levels to inhibit PD-1 and CD8 + T cell activation (Benghalem et al, 2017), indicating that reduction of IL-2 by HDL might be a doubleedged sword.…”

Section: T Cellsmentioning

confidence: 99%

Targeting HDL in tumor microenvironment: New hope for cancer therapy

Zhao

Zhu

Shi

et al. 2021

Journal Cellular Physiology

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Epidemiological studies have shown that plasma HDL-C levels are closely related to the risk of prostate cancer, breast cancer, and other malignancies. As one of the key carriers of cholesterol regulation, high-density lipoprotein (HDL) plays an important role in tumorigenesis and cancer development through anti-inflammation, antioxidation, immune-modulation, and mediating cholesterol transportation in cancer cells and noncancer cells. In addition, the occurrence and progression of cancer are closely related to the alteration of the tumor microenvironment (TME). Cancer cells synthesize and secrete a variety of cytokines and other factors to promote the reprogramming of surrounding cells and shape the microenvironment suitable for cancer survival. By analyzing the effect of HDL on the infiltrating immune cells in the TME, as well as the relationship between HDL and tumor-associated angiogenesis, it is suggested that a moderate increase in the level of HDL in vivo with consequent improvement of the function of HDL in the TME and induction of intracellular cholesterol efflux may be a promising strategy for cancer therapy.

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High-density lipoprotein immunomodulates the functional activities of macrophage and cytokines produced during ex vivo macrophage-CD4 + T cell crosstalk at the recent-onset human type 1 diabetes

Cited by 10 publications

References 89 publications

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

Immunometabolic factors in adolescent chronic disease are associated with Th1 skewing of invariant Natural Killer T cells

Targeting HDL in tumor microenvironment: New hope for cancer therapy

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