Basophils control T-cell responses and limit disease activity in experimental murine colitis
Basophils control T-cell responses and limit disease activity in experimental murine colitis
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DOI：
10.1038/mi.2013.38
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发表时间：
2014-01-01
影响因子：
8
通讯作者：
Mack, M.
中科院分区：
文献类型：
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作者：
Gomez, M. Rodriguez;Talke, Y.;Mack, M.
嗜碱性粒细胞已被认为是辅助性T细胞2型（Th 2）反应的重要诱导剂。使用过继转移CD 4（+）CD 62 L（+）T细胞进入淋巴细胞减少宿主的结肠炎模型，我们分析了嗜碱性粒细胞如何调节T细胞应答和调节疾病活动。转移的T细胞迅速增殖，产生大量的白细胞介素（IL）-3，并以IL-3依赖的方式扩增嗜碱性粒细胞的数量。在第8天，用两种不同的抗体消耗嗜碱性粒细胞显著上调了转移的T细胞中的Th 1细胞因子。增加的Th 1细胞因子表达持续到实验结束时，嗜碱性粒细胞耗竭的小鼠表现出结肠炎的恶化，伴随更严重的体重减轻、组织学损伤、结肠白细胞浸润和促炎细胞因子的表达。在体外，我们发现嗜碱性粒细胞衍生的IL-4和IL-6下调干扰素-γ，IL-2和肿瘤坏死因子在T细胞中的表达。这些数据显示嗜碱性粒细胞在T细胞驱动的自身免疫模型中的有益作用。
Basophils have been recognized as important inducers of T helper type 2 (Th2) responses. Using the colitis model of adoptive transfer of CD4(+) CD62L(+) T cells into lymphopenic hosts, we have analyzed how basophils regulate T-cell responses and modulate disease activity. Transferred T cells rapidly proliferate, produce large amounts of interleukin (IL)-3, and expand the number of basophils in an IL-3-dependent manner. Depletion of basophils with two different antibodies substantially upregulated Th1 cytokines in transferred T cells at day 8. Increased Th1 cytokine expression persisted until the end of the experiment when basophil-depleted mice showed exacerbation of colitis with more severe loss of weight, histological damage, colonic leukocyte infiltration, and expression of pro-inflammatory cytokines. In vitro, we show that basophil-derived IL-4 and IL-6 downregulates expression of interferon-gamma, IL-2, and tumor necrosis factor in T cells. These data show a beneficial role of basophils in a T-cell driven model of autoimmunity.