Upregulated adenosine 2A receptor accelerates post-infectious irritable bowel syndrome by promoting CD4+ T cells' T helper 17 polarization.
Upregulated adenosine 2A receptor accelerates post-infectious irritable bowel syndrome by promoting CD4+ T cells' T helper 17 polarization.
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DOI：
10.3748/wjg.v28.i25.2955
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发表时间：
2022-07-07
影响因子：
4.3
通讯作者：
Lan, Cheng
中科院分区：
文献类型：
--
作者：
Dong, Li-Wei;Ma, Zhi-Chao;Fu, Jiao;Huang, Bai-Li;Liu, Fu-Jin;Sun, Deming;Lan, Cheng
关键词：
背景感染后肠易激综合征（PI-IBS）通常被认为是一种功能性疾病。最近的几项研究报道了PI-IBS中的低度炎症和免疫功能障碍的参与。T辅助细胞17（Th 17）极化发生在IBS中。腺苷及其受体参与肠道炎症和免疫调节。目的探讨腺苷2A受体（adenosine 2A receptor，A2 AR）调控的CD 4 + T细胞Th 17极化在PI-IBS发病中的作用。方法用旋毛虫感染小鼠建立PI-IBS模型。免疫组化法检测肠道A2 AR和CD 4 + T淋巴细胞，酶联免疫法检测炎症细胞因子。分离存在于动物脾脏中的CD 4 + T淋巴细胞，并与或不与A2 AR激动剂和拮抗剂一起培养。Western blotting和实时定量聚合酶链反应检测A2 AR对细胞和肠组织的影响。测定细胞因子产生。还评估了A2 AR相关信号通路分子的蛋白质和mRNA水平。同时，给小鼠注射A2 AR激动剂和拮抗剂，观察其临床表现。结果PI-IBS小鼠模型中ATP和A2 AR表达增加（P < 0.05），抑制A2 AR可改善PI-IBS的临床表现，包括腹缩反射和结肠运输试验（P < 0.05）。PI-IBS时肠道CD 4 + T细胞数量和IL-17蛋白水平升高，A2 AR拮抗剂可逆转PI-IBS时肠道CD 4 + T细胞数量和IL-17蛋白水平的升高（P < 0.05）。CD 4 + T细胞在体外表达A2 AR并产生IL-17，其表达受A2 AR激动剂和拮抗剂的调节。A2 AR拮抗剂通过Janus激酶-信号转导子和转录激活子-受体相关孤儿受体γ信号通路增加CD 4 + T细胞产生IL-17。结论A2 AR表达上调可能通过促进CD 4 + T细胞Th 17极化而增强PI-IBS。
BACKGROUND Post-infectious irritable bowel syndrome (PI-IBS) is generally regarded as a functional disease. Several recent studies have reported the involvement of low-grade inflammation and immunological dysfunction in PI-IBS. T helper 17 (Th17) polarization occurs in IBS. Adenosine and its receptors participate in intestinal inflammation and immune regulation. AIM To investigate the role of Th17 polarization of CD4+ T cells regulated by adenosine 2A receptor (A2AR) in PI-IBS. METHODS A PI-IBS model was established by infecting mice with Trichinella spiralis. The intestinal A2AR and CD4+ T lymphocytes were detected by immunohistochemistry, and the inflammatory cytokines were detected by enzyme-linked immunoassay. CD4+ T lymphocytes present in the animal’s spleen were separated and cultured with or without A2AR agonist and antagonist. Western blotting and real-time quantitative polymerase chain reaction were performed to determine the effect of A2AR on the cells and intestinal tissue. Cytokine production was determined. The protein and mRNA levels of A2AR associated signaling pathway molecules were also evaluated. Furthermore, A2AR agonist and antagonist were injected into the mouse model and the clinical features were observed. RESULTS The PI-IBS mouse model showed increased expression of ATP and A2AR (P < 0.05), and inhibition of A2AR improved the clinical features in PI-IBS, including the abdominal withdrawal reflex and colon transportation test (P < 0.05). The number of intestinal CD4+ T cells and interleukin-17 (IL-17) protein levels increased during PI-IBS, which was reversed by administration of the A2AR antagonist (P < 0.05). CD4+ T cells expressed A2AR and produced IL-17 in vitro, which was regulated by the A2AR agonist and antagonist. The A2AR antagonist increased the production of IL-17 by CD4+ T cells via the Janus kinase-signal transducer and activator of transcription-receptor-related orphan receptor γ signaling pathway. CONCLUSION The results of the present study suggested that the upregulation of A2AR increases PI-IBS by promoting the Th17 polarization of CD4+ T cells.
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影响因子：
5.6
作者：
Burnstock G
通讯作者：
Burnstock G
DOI：
10.4049/jimmunol.1001567
发表时间：
2011-02-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Belikoff BG;Hatfield S;Georgiev P;Ohta A;Lukashev D;Buras JA;Remick DG;Sitkovsky M
通讯作者：
Sitkovsky M
影响因子：
3.5
作者：
Hou, Tengfei;Xiang, Hongchun;Li, Man
通讯作者：
Li, Man
DOI：
10.1038/nrgastro.2015.121
发表时间：
2015-10
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1007/s00109-017-1545-1
发表时间：
2017-09
期刊：
Journal of molecular medicine (Berlin, Germany)
影响因子：
--
作者：
Longhi MS;Moss A;Jiang ZG;Robson SC
通讯作者：
Robson SC