Retinoic Acid Induces Functionally Suppressive Foxp3(+)RORγt(+) T Cells In Vitro.
Retinoic Acid Induces Functionally Suppressive Foxp3(+)RORγt(+) T Cells In Vitro.
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DOI：
10.3389/fimmu.2021.675733
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发表时间：
2021
影响因子：
7.3
通讯作者：
López-Fandiño R
中科院分区：
文献类型：
--
作者：
Martínez-Blanco M;Lozano-Ojalvo D;Pérez-Rodríguez L;Benedé S;Molina E;López-Fandiño R
共表达Foxp 3和RORγt的具有调节功能的CD 4 + T细胞与小鼠对无害食物抗原的口服耐受性的发展有关。本研究旨在了解IL-6和视黄酸（RA）在Foxp 3 +RORγt+ T细胞体外生成中的作用，并研究此类细胞是否具有抑制特性。从BALB/c小鼠的脾脏分离的CD 4 + CD 25- T细胞在单独的IL-2或与TFG-β和不同浓度的IL-6和/或RA一起存在下刺激。在不同时间点评估总CD 4 + T细胞群中Foxp 3+、ROR γt+、IL-17+、Foxp 3 + RORγt-、Foxp 3 +RORγt+和Foxp 3-RORγt+ T细胞的百分比、细胞因子（IL-10和IL-17 A）的产生和基因表达（Foxp 3、Rorc、Tgfb 1、Il 6、Il 10和Il 17）。评估了在RA存在下由CD 4 + CD 44-CD 62 L+细胞产生的细胞的表型和抑制效应T细胞增殖的能力。在孵育期开始时，TGF-β加IL-6诱导Foxp 3+和双阳性Foxp 3 +RORγt+ T细胞的产生的程度高于单独的TGF-β，尽管Foxp 3的表达随后下降。RA与TGF-β联合应用可增加Foxp 3和Rorc表达以及Foxp 3和RORγt转录，并促进表达和分泌IL-17的Foxp 3 +RORγt-和Foxp 3 +RORγt+细胞的分化。在RA存在下体外产生的Foxp 3 + T细胞具有功能抑制性。在IL-2和TGF-β的影响下，可以在体外产生表达和分泌IL-17的抑制性Foxp 3 +RORγt+ T细胞，RA进一步有助于稳定这种表型。
CD4+ T cells with regulatory function co-expressing Foxp3 and RORγt are linked to the development of oral tolerance towards innocuous food antigens in mice. This study aimed to discern the role played by IL-6 and retinoic acid (RA) in the in vitro generation of Foxp3+RORγt+ T cells and to investigate whether such cells have suppressive properties. CD4+CD25- T cells isolated from the spleen of BALB/c mice, were stimulated in the presence of IL-2 alone or together with TFG-β and different concentrations of IL-6 and/or RA. Percentage of Foxp3+, RORγt+, IL-17+, Foxp3+RORγt-, Foxp3+RORγt+, and Foxp3-RORγt+ T cells within the total CD4+ T cell population, production of cytokines (IL-10 and IL-17A) and gene expression (Foxp3, Rorc, Tgfb1, Il6, Il10, and Il17) were assessed at different time points. The phenotype and ability of cells generated from CD4+CD44-CD62L+ cells in the presence of RA to suppress effector T cell proliferation was assessed. TGF-β plus IL-6 induced the generation of Foxp3+ and double positive Foxp3+RORγt+ T cells to a higher extent than TGF-β alone at the beginning of the incubation period, although expression of Foxp3 subsequently declined. RA, added to TGF-β, increased Foxp3 and Rorc expression and Foxp3 and RORγt transcription and promoted the differentiation of Foxp3+RORγt- and Foxp3+RORγt+ cells that expressed and secreted IL-17. Foxp3+ T cells generated in vitro in presence of RA were functionally suppressive. Under the influence of IL-2 and TGF-β, suppressive Foxp3+RORγt+ T cells that express and secrete IL-17 can be produced in vitro and RA further contributes to stabilize this phenotype.
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DOI：
10.1016/j.jaci.2016.06.003
发表时间：
2016-09
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Noval Rivas M;Chatila TA
通讯作者：
Chatila TA
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
32.4
作者：
Veldhoen, M;Hocking, RJ;Stockinger, B
通讯作者：
Stockinger, B
影响因子：
32.4
作者：
Hill JA;Hall JA;Sun CM;Cai Q;Ghyselinck N;Chambon P;Belkaid Y;Mathis D;Benoist C
通讯作者：
Benoist C
影响因子：
56.9
作者：
Mucida, Daniel;Park, Yunji;Cheroutre, Hilde
通讯作者：
Cheroutre, Hilde