Estrogen receptor α/HDAC/NFAT axis for delphinidin effects on proliferation and differentiation of T lymphocytes from patients with cardiovascular risks

• Published in: Scientific reports Vol. 7; no. 1; pp. 9378 - 17
• Main Authors: Dayoub, Ousama, Le Lay, Soazig, Soleti, Raffaella, Clere, Nicolas, Hilairet, Gregory, Dubois, Séverine, Gagnadoux, Frédéric, Boursier, Jérôme, Martínez, Maria Carmen, Andriantsitohaina, Ramaroson
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.08.2017; Nature Publishing Group
• Subjects: 13/2; 631/250/127; 692/699/2743/2037; 96/31; 96/34; 96/95; Anthocyanins - pharmacology; Calcium - metabolism; Calcium influx; Calcium Signaling - drug effects; Calcium signalling; Cardiovascular diseases; Cardiovascular Diseases - etiology; Cardiovascular Diseases - metabolism; Cell activation; Cell Cycle - drug effects; Cell Differentiation - drug effects; Cell proliferation; Cell Proliferation - drug effects; Cells, Cultured; Clonal deletion; Endothelium; Estrogen Receptor alpha - metabolism; Estrogen receptors; Estrogens; Fulvestrant; Health risks; Helper cells; Histone deacetylase; Histone Deacetylases - metabolism; Human health and pathology; Humanities and Social Sciences; Humans; Immune response; Inflammation; Life Sciences; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; MAP Kinase Signaling System - drug effects; Metabolic disorders; Metabolic syndrome; multidisciplinary; NF-AT protein; NFATC Transcription Factors - metabolism; Obesity; Risk Factors; Science; Science (multidisciplinary); Signal Transduction - drug effects; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes - cytology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Wine
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-09933-4

Delphinidin, an anthocyanin present in red wine, has been reported to preserve the integrity of endothelium via an estrogen receptor alpha (ERα)-dependent mechanism. However, the effect of delphinidin on the immune response in obesity-related inflammation remains unknown. Given the important role of T lymphocytes in obesity-related inflammation, we investigated the effect of delphinidin on proliferation and differentiation of T lymphocytes from healthy subjects and metabolic syndrome patients. Delphinidin decreased the proliferation stimulated by different agents acting through different mechanisms. This effect of delphinidin was associated with its ability to inhibit Ca 2+ signaling via reduced store-operated Ca 2+ entry and release, and subsequent decrease of HDAC and NFAT activations. Delphinidin also inhibited ERK1/2 activation. Pharmacological inhibition of ER with fulvestrant, or deletion of ERα, prevented the effect of delphinidin. Further, delphinidin suppressed the differentiation of T cells toward Th1, Th17 and Treg without affecting Th2 subsets. Interestingly, delphinidin inhibited both proliferation and differentiation of T cells taken from patients with cardiovascular risks associated with metabolic syndrome. Together, we propose that delphinidin, by acting on ERα via multiple cellular targets, may represent a new approach against chronic inflammation associated with T lymphocyte activation, proliferation and differentiation, in patients with cardiovascular risk factors.