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首页> 外文期刊>The Journal of Immunology: Official Journal of the American Association of Immunologists >Cytokine-induced alterations of alpha7 nicotinic receptor in colonic CD4 T cells mediate dichotomous response to nicotine in murine models of Th1/Th17- versus Th2-mediated colitis.
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Cytokine-induced alterations of alpha7 nicotinic receptor in colonic CD4 T cells mediate dichotomous response to nicotine in murine models of Th1/Th17- versus Th2-mediated colitis.

机译：在Th1 / Th17-与Th2介导的结肠炎小鼠模型中，结肠素CD4 T细胞中细胞因子诱导的α7烟碱样受体受体的改变介导了对烟碱的二分反应。

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摘要

Ulcerative colitis (UC) and Crohn's disease (CD) are two forms of chronic inflammatory bowel disease. CD4 T cells play a central role in the pathogenesis of both diseases. Smoking affects both UC and CD but with opposite effects, ameliorating UC and worsening CD. We hypothesized that the severity of gut inflammation could be modulated through T cell nicotinic acetylcholine receptors (nAChRs) and that the exact clinical outcome would depend on the repertoire of nAChRs on CD4 T cells mediating each form of colitis. We measured clinical and immunologic outcomes of treating BALB/c mice with oxazolone- and trinitrobenzene sulfonic acid (TNBS)-induced colitides by nicotine. Nicotine attenuated oxazolone colitis, which was associated with an increased percentage of colonic regulatory T cells and a reduction of Th17 cells. TCR stimulation of naive CD4(+)CD62L(+) T cells in the presence of nicotine upregulated expression of Foxp3. In marked contrast, nicotine worsened TNBS colitis, and this was associated with increased Th17 cells among colonic CD4 T cells. Nicotine upregulated IL-10 and inhibited IL-17 production, which could be abolished by exogenous IL-12 that also abolished the nicotine-dependent upregulation of regulatory T cells. The dichotomous action of nicotine resulted from the up- and downregulation of anti-inflammatory alpha7 nAChR on colonic CD4 T cells induced by cytokines characteristic of the inflammatory milieu in oxazolone (IL-4) and TNBS (IL-12) colitis, respectively. These findings help explain the dichotomous effect of smoking in patients with UC and CD, and they underscore the potential for nicotinergic drugs in regulating colonic inflammation.
机译：溃疡性结肠炎（UC）和克罗恩氏病（CD）是慢性炎症性肠病的两种形式。 CD4 T细胞在两种疾病的发病机理中都起着核心作用。吸烟会影响UC和CD，但作用相反，可改善UC和使CD恶化。我们假设肠道炎症的严重程度可以通过T细胞烟碱乙酰胆碱受体（nAChRs）进行调节，确切的临床结果将取决于nAChRs在介导每种结肠炎的CD4 T细胞上的组成。我们测量了尼古丁用恶唑酮和三硝基苯磺酸（TNBS）诱导的大肠菌素治疗BALB / c小鼠的临床和免疫学结果。尼古丁减轻了恶唑酮结肠炎，这与结肠调节性T细胞百分比增加和Th17细胞减少有关。在尼古丁上调Foxp3表达的情况下，TCR刺激幼稚CD4（+）CD62L（+）T细胞。形成鲜明对比的是，尼古丁使TNBS结肠炎恶化，这与结肠CD4 T细胞中Th17细胞增加有关。尼古丁上调了IL-10并抑制了IL-17的产生，这可以被外源性IL-12消除，后者也消除了尼古丁依赖性的调节性T细胞上调。尼古丁的二分作用是分别由恶唑酮（IL-4）和TNBS（IL-12）结肠炎中炎性环境的细胞因子诱导的结肠炎CD4 T细胞上抗炎性α7nAChR的上调和下调引起的。这些发现有助于解释吸烟对UC和CD患者的二分作用，并且强调了烟碱能药物在调节结肠炎症中的潜力。

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