Functional characterization of interleukin 4 and retinoic acid signaling crosstalk during alternative macrophage activation

Pinos, Ivan; Yu, Jianshi; Pilli, Nageswara; Kane, Maureen A.; Amengual, Jaume

doi:10.1016/j.bbalip.2023.159291

Cited by 4 publications

(6 citation statements)

References 86 publications

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“…We also demonstrated that exogenous retinoic synergizes with interleukin 4 (IL4) to stimulate the expression of anti-inflammatory genes in the macrophage, including arginase 1. More importantly, we observed that macrophages exposed to both retinoic acid and IL4 displayed greater efferocytosis and lysosomal activities than those exposed to IL4 or retinoic acid alone [43]. These results indicate that the combination of retinoic acid with anti-inflammatory signals typically present during inflammatory resolution such as IL4 could favor atherosclerosis resolution.…”

Section: Discussionmentioning

confidence: 94%

“…The presence of anti-inflammatory macrophages in the lesions, together with a net egress of pro- inflammatory macrophages, are key features of atherosclerosis resolution [41]. We quantified arginase 1 content in the lesion, a key anti-inflammatory marker in mice that contributes to collagen synthesis [42], and is synergistically upregulated in anti-inflammatory macrophages exposed to retinoic acid [43, 44] (Figure 5F). Only those mice fed β-carotene, independent of the injection with IgG or anti-CD25, showed an upregulation of arginase 1 in the lesion (Figure 5G).…”

Section: Resultsmentioning

confidence: 99%

“…This hypothesis has not been demonstrated to date, partially due to the technical difficulty to quantify retinoic acid production in biological samples [76]. We recently overcame this limitation and demonstrated for the first time that alternatively-activated macrophages produce and release retinoic acid in a STAT6-dependent manner [44]. We also demonstrated that exogenous retinoic synergizes with interleukin 4 (IL4) to stimulate the expression of arginase 1, which is considered an anti-inflammatory marker in murine macrophages [44, 77].…”

Section: Discussionmentioning

confidence: 99%

“…We recently overcame this limitation and demonstrated for the first time that alternatively-activated macrophages produce and release retinoic acid in a STAT6-dependent manner [44]. We also demonstrated that exogenous retinoic synergizes with interleukin 4 (IL4) to stimulate the expression of arginase 1, which is considered an anti-inflammatory marker in murine macrophages [44, 77]. Arginase 1 catalyzes the production of ornithine, which is a precursor of proline [42].…”

Section: Discussionmentioning

confidence: 99%

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β-carotene accelerates the resolution of atherosclerosis in mice

Pinos

Coronel

Albakri

et al. 2023

Preprint

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β-carotene oxygenase 1 (BCO1) catalyzes the cleavage of β-carotene to form vitamin A. Besides its role in vision, vitamin A regulates the expression of genes involved in lipid metabolism and immune cell differentiation. BCO1 activity is associated with the reduction of plasma cholesterol in humans and mice, while dietary β-carotene reduces hepatic lipid secretion and delays atherosclerosis progression in various experimental models. Here we show that β-carotene also accelerates atherosclerosis resolution in two independent murine models, independently of changes in body weight gain or plasma lipid profile. Experiments inBco1-/-mice implicate vitamin A production in the effects of β-carotene on atherosclerosis resolution. To explore the direct implication of dietary β-carotene on regulatory T cells (Tregs) differentiation, we utilized anti-CD25 monoclonal antibody infusions. Our data show that β-carotene favors Treg expansion in the plaque, and that the partial inhibition of Tregs mitigates the effect of β-carotene on atherosclerosis resolution. Our data highlight the potential of β-carotene and BCO1 activity in the resolution of atherosclerotic cardiovascular disease.

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Section: Discussionmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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β-carotene accelerates the resolution of atherosclerosis in mice

Pinos

Coronel

Albakri

et al. 2023

Preprint

Self Cite

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“…[397][398][399] IL4 induces retinol production and excretion in macrophages in a STAT6-dependent manner. 400 In contrast, retinoic acid is essential to convert immature myeloid cells to mature neutrophilic cells with vitamin A supplementation affecting predominantly migration and maturation of neutrophils 401 (Figure 4).…”

Section: Macrophages and Neutrophilsmentioning

confidence: 99%

Nutrition in chronic inflammatory conditions: Bypassing the mucosal block for micronutrients

Roth‐Walter,

Berni Canani,

O'Mahony

et al. 2023

Allergy

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Nutritional Immunity is one of the most ancient innate immune responses, during which the body can restrict nutrients availability to pathogens and restricts their uptake by the gut mucosa (mucosal block). Though this can be a beneficial strategy during infection, it also is associated with non‐communicable diseases—where the pathogen is missing; leading to increased morbidity and mortality as micronutritional uptake and distribution in the body is hindered. Here, we discuss the acute immune response in respect to nutrients, the opposing nutritional demands of regulatory and inflammatory cells and particularly focus on some nutrients linked with inflammation such as iron, vitamins A, Bs, C, and other antioxidants. We propose that while the absorption of certain micronutrients is hindered during inflammation, the dietary lymph path remains available. As such, several clinical trials investigated the role of the lymphatic system during protein absorption, following a ketogenic diet and an increased intake of antioxidants, vitamins, and minerals, in reducing inflammation and ameliorating disease.

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β-Carotene accelerates the resolution of atherosclerosis in mice

Pinos

Coronel

Albakri

et al. 2024

eLife

View full text Add to dashboard Cite

β-carotene oxygenase 1 (BCO1) catalyzes the cleavage of β-carotene to form vitamin A. Besides its role in vision, vitamin A regulates the expression of genes involved in lipid metabolism and immune cell differentiation. BCO1 activity is associated with the reduction of plasma cholesterol in humans and mice, while dietary β-carotene reduces hepatic lipid secretion and delays atherosclerosis progression in various experimental models. Here we show that β-carotene also accelerates atherosclerosis resolution in two independent murine models, independently of changes in body weight gain or plasma lipid profile. Experiments in Bco1-/- mice implicate vitamin A production in the effects of β-carotene on atherosclerosis resolution. To explore the direct implication of dietary β-carotene on regulatory T cells (Tregs) differentiation, we utilized anti-CD25 monoclonal antibody infusions. Our data show that β-carotene favors Treg expansion in the plaque, and that the partial inhibition of Tregs mitigates the effect of β-carotene on atherosclerosis resolution. Our data highlight the potential of β-carotene and BCO1 activity in the resolution of atherosclerotic cardiovascular disease.

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Functional characterization of interleukin 4 and retinoic acid signaling crosstalk during alternative macrophage activation

Cited by 4 publications

References 86 publications

β-carotene accelerates the resolution of atherosclerosis in mice

β-carotene accelerates the resolution of atherosclerosis in mice

Nutrition in chronic inflammatory conditions: Bypassing the mucosal block for micronutrients

β-Carotene accelerates the resolution of atherosclerosis in mice

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