IL-21 and IRF4: A Complex Partnership in Immune and Metabolic Regulation

Knudsen, Nelson H.; Lee, Chih‐Hao

doi:10.2337/db14-0273

Cited by 8 publications

(3 citation statements)

References 13 publications

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“…In parallel, Treg cells were more abundant in IL-21 knockout mice in comparison to wild type animals fed both normal diet and HFD. These results have been confirmed by Knudsen and Lee [ 41 ] who demonstrated that IL-21 is a major negative regulator of interferon regulatory factor 4, thus inhibiting Treg cell accumulation in adipose tissue and systemic insulin sensitivity. Increase in IL-17 and IL-21/22 in the liver of HFD mice has been reported by Cavallari et al [ 42 ].…”

Section: Discussionsupporting

confidence: 67%

Immune Profile of Obese People and In Vitro Effects of Red Grape Polyphenols on Peripheral Blood Mononuclear Cells

Magrone

Jirillo

Spagnoletta

et al. 2017

Oxidative Medicine and Cellular Longevity

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The in vitro ability of polyphenols, extracted from red grape, to modulate peripheral blood mononuclear cell responses has been evaluated in 20 obese (Ob) people. With regard to cytokine release in response to phorbol myristate acetate (PMA), levels of interleukin-2 (IL-2), interferon-γ (IFN-γ), IL-4, IL-10, and IL-17 were higher in the Ob than in healthy (H) subjects. Vice versa, IL-21 concentrations were detected only in H people but they were undetectable in the Ob counterpart. In general terms, levels of IL-1β, IL-6, IL-8, and tumor necrosis factor-α were higher in Ob people when compared to H controls. On the other hand, polyphenols did not modify IFN-γ, IL-4, and IL-17 levels. However, an increase in IL-2 was observed in H individuals, whereas its levels were decreased in the Ob counterpart. Polyphenols significantly increased IL-10 release from H donors, whereas a trend to increase was observed in Ob people. In addition, polyphenols were able to significantly increase levels of H IL-21, while this was not the case in Ob people. Since IL-21 is an inducer of Th17 cells, it is likely that polyphenols may suppress the sources of this cytokine via production of IL-10. Accordingly, polyphenols decreased IL-1β and IL-6 release in comparison to H controls.

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Section: Discussionsupporting

confidence: 67%

Immune Profile of Obese People and In Vitro Effects of Red Grape Polyphenols on Peripheral Blood Mononuclear Cells

Magrone

Jirillo

Spagnoletta

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…35 The association between immunosenescence and cardiovascular morbidity could be ambidirectional, explained by the switch in immune phenotype from anti-inflammatory to a pro-inflammatory profile in metabolic disorders, and the reduction of insulin sensitivity by pro-inflammatory cytokines in inflammatory disorders. 36 CD4þ CD28null T cells have been associated with endothelial dysfunction in RA patients. 37 In addition, CD4þCD28null are increased in end-stage renal disease patients (ESRD), mainly in those with cytomegalovirus infection, compared with healthy donors.…”

Section: Discussionmentioning

confidence: 99%

Circulating CD4+CD28null and extra-thymic CD4+CD8+ double positive T cells are independently associated with disease damage in systemic lupus erythematosus patients

Ugarte‐Gil

Sánchez-Zúñiga

Gamboa-Cárdenas

et al. 2015

Lupus

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“…Compared with wildtype mice fed with HFD, Il21 or Stat3 knockout mice fed with HFD have increased accumulation of VAT Treg cells and improved insulin sensitivity but decreased adipose inflammation [58,60]. Further studies have suggested that in obesity state, the level of interferon regulatory factor 4 (IRF4, a transcriptional regulator of fasting lipolysis in adipose tissue [61,62]) is negatively regulated by IL-21 and it might correlate with the decrease of VAT Treg cells [58,61].…”

Section: Other Regulatorsmentioning

confidence: 99%

Tissue adaptation of regulatory T cells in adipose tissue

Bai

et al. 2022

Eur J Immunol

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Foxp3 + regulatory T (Treg) cells critically suppress over-activated immune responses and therefore maintain immune homeostasis. Adipose tissue-resident Treg (AT Treg) cells are known for modulating immunity and metabolism in adipose tissue microenvironment through various physiological signals, as well as their heterogeneous subsets, which potentially play disparate roles in aging and obesity. Recent single-cell studies of Treg cells have revealed specialized trajectories of their tissue adaptation and development in lymphoid tissues and at barrier sites. Here, we reviewed a T Cell Receptor (TCR)-primed environmental cue-boosted model of adipose Treg cells' tissue adaptation, especially in response to IL-33, IFN-α, insulin, and androgen signals, which trigger sophisticated transcriptional cascades and ultimately establish unique transcriptional modules in adipose Treg cell subsets. In addition, we further discuss potential therapeutic strategies against aging and obesity by blocking detrimental environmental cues, strengthening the functions of specific AT Treg subsets and modifying the communications between AT Treg subsets and adipocytes.

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IL-21 and IRF4: A Complex Partnership in Immune and Metabolic Regulation

Cited by 8 publications

References 13 publications

Immune Profile of Obese People and In Vitro Effects of Red Grape Polyphenols on Peripheral Blood Mononuclear Cells

Immune Profile of Obese People and In Vitro Effects of Red Grape Polyphenols on Peripheral Blood Mononuclear Cells

Circulating CD4+CD28null and extra-thymic CD4+CD8+ double positive T cells are independently associated with disease damage in systemic lupus erythematosus patients

Tissue adaptation of regulatory T cells in adipose tissue

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