Essential role of CD11a in CD8+ T-cell accumulation and activation in adipose tissue.
Essential role of CD11a in CD8+ T-cell accumulation and activation in adipose tissue.
复制标题
DOI：
10.1161/atvbaha.113.302077
复制
发表时间：
2014-01
期刊：
影响因子：
--
通讯作者：
Wu H
中科院分区：
文献类型：
--
作者：
Jiang E;Perrard XD;Yang D;Khan IM;Perrard JL;Smith CW;Ballantyne CM;Wu H
T细胞，特别是CD 8 + T细胞，是肥胖相关脂肪组织（AT）炎症的主要参与者。我们研究了AT中CD 8 + T细胞聚集和活化的机制以及CD 11 a，β2整合素的作用。肥胖小鼠AT中的CD 8 + T细胞表现出活化的表型，增殖和干扰素-γ表达增加。在体外，来自小鼠AT的CD 8 + T细胞显示出增加的干扰素-γ表达和对白细胞介素-12和白细胞介素-18刺激的增殖，其在肥胖AT中增加。在肥胖小鼠中，CD 8 + T细胞中的CD 11 a上调。在肥胖小鼠中，CD 11 a的消融显著降低了AT中的T细胞积聚、活化和增殖。连续转移表明，来自野生型小鼠的CD 8 + T细胞，而不是来自CD 11 a缺陷型小鼠的，浸润到受体肥胖野生型小鼠的AT中。CD 11 a缺乏还减少AT中产生肿瘤坏死因子α和白细胞介素12的巨噬细胞，并改善胰岛素抵抗。肥胖AT中细胞因子的联合作用诱导局部CD 8 + T细胞的增殖反应，其沿着增加的浸润，有助于AT中CD 8 + T细胞的积聚和活化。CD 11 a通过参与T细胞浸润和活化在AT炎症中起关键作用。
T cells, particularly CD8+ T cells, are major participants in obesity-linked adipose tissue (AT) inflammation. We examined the mechanisms of CD8+ T-cell accumulation and activation in AT and the role of CD11a, a β2 integrin. CD8+ T cells in AT of obese mice showed activated phenotypes with increased proliferation and interferon-γ expression. In vitro, CD8+ T cells from mouse AT displayed increased interferon-γ expression and proliferation to stimulation with interleukin-12 and interleukin-18, which were increased in obese AT. CD11a was upregulated in CD8+ T cells in obese mice. Ablation of CD11a in obese mice dramatically reduced T-cell accumulation, activation, and proliferation in AT. Adoptive transfer showed that CD8+ T cells from wild-type mice, but not from CD11a-deficient mice, infiltrated into AT of recipient obese wild-type mice. CD11a deficiency also reduced tumor necrosis factor-α–producing and interleukin-12–producing macrophages in AT and improved insulin resistance. Combined action of cytokines in obese AT induces proliferative response of CD8+ T cells locally, which, along with increased infiltration, contributes to CD8+ T-cell accumulation and activation in AT. CD11a plays a crucial role in AT inflammation by participating in T-cell infiltration and activation.