From the Departments of Medicine (E.J., X.D.P., D.Y., I.M.K., J.L.P., C.M.B., H.W.) and Pediatrics (C.W.S., C.M.B., H.W.), Baylor College of Medicine, Houston, TX; and Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, The Methodist Hospital, Houston, TX (C.M.B.).
Arterioscler Thromb Vasc Biol. 2014 Jan;34(1):34-43. doi: 10.1161/ATVBAHA.113.302077. Epub 2013 Oct 24.
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.
T 细胞，尤其是 CD8(+)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 CD8(+)T 细胞在 AT 中的积累和激活机制以及 CD11a（一种β2 整合素）的作用。
肥胖小鼠 AT 中的 CD8(+)T 细胞表现出激活表型，增殖和干扰素-γ表达增加。在体外，肥胖 AT 中增加的白细胞介素 12 和白细胞介素 18 刺激下，来自肥胖 AT 的 CD8(+)T 细胞表现出增加的干扰素-γ表达和增殖。CD8(+)T 细胞中 CD11a 上调。肥胖小鼠中 CD11a 的缺失显著减少了 AT 中的 T 细胞积累、激活和增殖。过继转移显示，来自野生型小鼠的 CD8(+)T 细胞，但不是来自 CD11a 缺陷型小鼠的 CD8(+)T 细胞，浸润到接受肥胖野生型小鼠的 AT 中。CD11a 缺陷也减少了 AT 中肿瘤坏死因子-α产生和白细胞介素-12 产生的巨噬细胞，并改善了胰岛素抵抗。
肥胖 AT 中的细胞因子的联合作用诱导 CD8(+)T 细胞在局部产生增殖反应，这与浸润增加一起导致 AT 中 CD8(+)T 细胞的积累和激活。CD11a 通过参与 T 细胞浸润和激活在 AT 炎症中发挥关键作用。
