Increased levels of Th17 cells are associated with non-neuronal acetylcholine in COPD patients

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• 作者：Mirella Profita^a ; ^{profita@ibim.cnr.it" class="auth_mail} ; Giusy Daniela Albano^a ; ^b ; Loredana Riccobono^a ; Caterina Di Sano^a ; Angela Marina Montalbano^a ; Rosalia Gagliardo^a ; Giulia Anzalone^a ; Anna Bonanno^a ; Michael Paul Pieper^c ; Mark Gjomarkaj^a
• 关键词：ACh ; acetylcholine ; COPD ; chronic obstructive pulmonary disease ; CSE ; cigarette smoke extract ; FOXP3 ; Forkhead family transcription factor ; HCh ; hemicholinium ; IL-17 ; Interleukin-17 ; mAChRs ; muscarinic receptors ; nAChRs ; nicotinic receptors ; PBMC ; peripheral blood mononuclear cells ; ROR纬t ; retinoic acid-related orphan receptor 纬t ; Th ; T helper
• 刊名：Immunobiology
• 出版年：May, 2014
• 年：2014
• 卷：219
• 期：5
• 页码：392-401
• 全文大小：2213 K

文摘

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Abstracts

T-lymphocytes, including Th17-cells and T-cells expressing acetylcholine (ACh), are key components of systemic inflammation in chronic obstructive pulmonary disease (COPD). We investigated whether ACh promotes Th17 cells in COPD.

ACh, IL-17A, IL-22, ROR纬t, FOXP3 expression and AChIL-17A, AChIL-22, AChROR纬t coexpression was evaluated in peripheral blood mononuclear cells (PBMC) from COPD patients (n = 16), healthy smokers (HS) (n = 12) and healthy control subjects (HC) (n = 13) (cultured for 48 h with PMA) by flow cytometry. Furthermore, we studied the effect of Tiotropium (Spiriva^庐) (100 nM) and Olodaterol (1 nM) alone or in combination, and of hemicholinium-3 (50 渭M) on AChIL-17A, AChIL-22, AChROR纬t, and FOXP3 expression in CD3⁺PBT-cells of PBMC from COPD patients (n = 6) cultured for 48 h with PMA.

CD3⁺PBT-cells expressing ACh, IL-17A, IL-22 and ROR纬t together with CD3⁺PBT-cells co-expressing AChIL-17A, AChIL-22 and AChROR纬t were significantly increased in COPD patients compared to HC and HS subjects with higher levels in HS than in HC without a significant difference. CD3⁺FOXP3⁺PBT-cells were increased in HS than in HC and COPD. Tiotropium and Olodaterol reduced the percentage of CD3⁺PBT-cells co-expressing AChIL-17A, AChIL-22, and AChROR纬t while increased the CD3⁺FOXP3⁺PBT-cells in PBMC from COPD patients, cultured in vitro for 48 h, with an additive effect when used in combination. Hemicholnium-3 reduced the percentage of ACh⁺IL-17A⁺, ACh⁺IL-22⁺, and ACh⁺ROR纬t⁺ while it did not affect FOXP3⁺ expression in CD3⁺PBT-cells from cultured PBMC from COPD patients.

We concluded that ACh might promote the increased levels of Th17-cells in systemic inflammation of COPD. Long-acting 尾2-agonists and anticholinergic drugs might contribute to control this event.