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Cigarette smoking induces human CCR6+Th17 lymphocytes senescence and VEGF-A secretion

Abstract : Chronic exposure to environmental pollutants is often associated with systemic inflammation. As such, cigarette smoking contributes to inflammation and lung diseases by inducing senescence of pulmonary cells such as pneumocytes, fibroblasts, and endothelial cells. Yet, how smoking worsens evolution of chronic inflammatory disorders associated with Th17 lymphocytes, such as rheumatoid arthritis, psoriasis, Crohn's disease, and multiple sclerosis, is largely unknown. Results from human studies show an increase in inflammatory CD4+ Th17 lymphocytes at blood- and pulmonary level in smokers. The aim of the study was to evaluate the sensitivity of CD4+ Th17 lymphocytes to cigarette smoke-induced senescence. Mucosa-homing CCR6+ Th17- were compared to CCR6neg -and regulatory T peripheral lymphocytes after exposure to cigarette smoke extract (CSE). Senescence sensitivity of CSE-exposed cells was assessed by determination of various senescence biomarkers (β-galactosidase activity, p16Ink4a- and p21 expression) and cytokines production. CCR6+ Th17 cells showed a higher sensitivity to CSE-induced senescence compared to controls, which is associated to oxidative stress and higher VEGFα secretion. Pharmacological targeting of ROS- and ERK1/2 signalling pathways prevented CSE-induced senescence of CCR6+Th17 lymphocytes as well as VEGFα secretion. Altogether, these results identify mechanisms by which pro-oxidant environmental pollutants contribute to pro-angiogenic and pathogenic CCR6+Th17 cells, therefore potential targets for therapeutic purposes.
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https://www.hal.inserm.fr/inserm-02874018
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Submitted on : Thursday, June 18, 2020 - 5:05:39 PM
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Indoumady Baskara, Stéphane Kerbrat, Maylis Dagouassat, Hoang Quy Nguyen, Maude Guillot-Delost, et al.. Cigarette smoking induces human CCR6+Th17 lymphocytes senescence and VEGF-A secretion. Scientific Reports, Nature Publishing Group, 2020, 10 (1), pp.6488. ⟨10.1038/s41598-020-63613-4⟩. ⟨inserm-02874018⟩

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