Intestinal CX3C chemokine receptor 1high (CX3CR1high) myeloid cells prevent T-cell-dependent colitis
Intestinal CX3C chemokine receptor 1high (CX3CR1high) myeloid cells prevent T-cell-dependent colitis
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DOI：
10.1073/pnas.1114931109
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发表时间：
2012-03-27
影响因子：
11.1
通讯作者：
Takeda, Kiyoshi
中科院分区：
文献类型：
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作者：
Kayama, Hisako;Ueda, Yoshiyasu;Takeda, Kiyoshi
CD4(+) T 淋巴细胞的充分激活对于宿主防御入侵病原体至关重要。然而，效应CD4(+) T细胞的过度活性会引起组织损伤，导致炎症性疾病，例如炎症性肠病。已经鉴定出肠道先天免疫细胞的几个独特亚群。然而，人们对先天免疫细胞亚群在抑制 T 细胞依赖性肠道炎症中的直接参与知之甚少。在此，我们报道肠道CX3C趋化因子受体1（高）（CX（3）CR1（高））CD11b（+）CD11c（+）细胞负责通过抑制T细胞反应来预防肠道炎症。这些细胞以细胞接触依赖性方式抑制CD4(+) T细胞增殖并预防T细胞依赖性结肠炎。如果没有 IL-10/Stat3 途径，抑制活性就会被消除。这些细胞通过两个步骤抑制 T 细胞增殖。最初，CX(3)CR1(high) CD11b(+) CD11c(+)细胞优先通过高表达的细胞间粘附分子-1/血管细胞粘附分子-1与T细胞相互作用；然后，由于 CD80/CD86 表达缺陷，它们无法激活 T 细胞。 IL-10/Stat3 途径介导 CD80/CD86 表达的减少。野生型 CX(3)CR1(high) CD11b(+) CD11c(+) 细胞的转移可防止骨髓特异性 Stat3 缺陷小鼠发生结肠炎。因此，这些细胞是调节性骨髓细胞
Adequate activation of CD4(+) T lymphocytes is essential for host defense against invading pathogens; however, exaggerated activity of effector CD4(+) T cells induces tissue damage, leading to inflammatory disorders such as inflammatory bowel diseases. Several unique subsets of intestinal innate immune cells have been identified. However, the direct involvement of innate immune cell subsets in the suppression of T-cell-dependent intestinal inflammation is poorly understood. Here, we report that intestinal CX3C chemokine receptor 1(high) (CX(3)CR1(high)) CD11b(+) CD11c(+) cells are responsible for prevention of intestinal inflammation through inhibition of T-cell responses. These cells inhibit CD4(+) T-cell proliferation in a cell contact-dependent manner and prevent T-cell-dependent colitis. The suppressive activity is abrogated in the absence of the IL-10/Stat3 pathway. These cells inhibit T-cell proliferation by two steps. Initially, CX(3)CR1(high) CD11b(+) CD11c(+) cells preferentially interact with T cells through highly expressed intercellular adhesion molecule-1/vascular cell adhesion molecule-1; then, they fail to activate T cells because of defective expression of CD80/CD86. The IL-10/Stat3 pathway mediates the reduction of CD80/CD86 expression. Transfer of wild-type CX(3)CR1(high) CD11b(+) CD11c(+) cells prevents development of colitis in myeloid-specific Stat3-deficient mice. Thus, these cells are regulatory myeloid