Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, J.B. Winsløwsvej 25, 5000 Odense C, Denmark.
Immunol Lett. 2017 Dec;192:72-78. doi: 10.1016/j.imlet.2017.10.012. Epub 2017 Oct 26.
Thymic dendritic cells (DC) play a role in central tolerance. Three thymic DC subtypes have been described: plasmacytoid DC (pDC) and two conventional DC (cDC), CD8α Sirpα DC and Sirpα CD8α cDC. Both pDC and Sirpα cDC can take up antigen in periphery and migrate into the thymus in response to chemokine signaling via CCR9 and CCR2 respectively. CCL2 is a major ligand for CCR2 and we previously showed that it was constitutively expressed in thymus, and that mice overexpressing CCL2 in thymus had reduced numbers of autoreactive T cells but elevated numbers of pDC. We have here investigated the role of CCL2-CCR2 axis in thymic pDC migration. We found that pDC expressed CCR2 at a high level and that their frequency was decreased in thymus, spleen and inguinal lymph nodes in mice lacking CCR2, but not in mice lacking CCL2. pDC migration towards the cortex or medulla within the thymus was not affected by CCL2 or CCR2 deficiency. Although some thymic progenitors expressed CCR2, this did not include those that give rise to pDC. Based on these results, we propose that CCR2 is involved in pDC homeostasis but its ligand CCL2 does not play a major role.
胸腺树突状细胞 (DC) 在中枢耐受中发挥作用。已经描述了三种胸腺 DC 亚型:浆细胞样 DC (pDC) 和两种常规 DC (cDC),CD8α Sirpα DC 和 Sirpα CD8α cDC。pDC 和 Sirpα cDC 都可以在外周摄取抗原,并分别通过趋化因子信号通过 CCR9 和 CCR2 迁移到胸腺中。CCL2 是 CCR2 的主要配体,我们之前表明它在胸腺中持续表达,并且在胸腺中过表达 CCL2 的小鼠中自身反应性 T 细胞的数量减少,但 pDC 的数量增加。我们在这里研究了 CCL2-CCR2 轴在胸腺 pDC 迁移中的作用。我们发现 pDC 高水平表达 CCR2,并且在缺乏 CCR2 的小鼠的胸腺、脾脏和腹股沟淋巴结中其频率降低,但在缺乏 CCL2 的小鼠中则不然。CCL2 或 CCR2 缺乏并不影响 pDC 向胸腺皮质或髓质的迁移。尽管一些胸腺祖细胞表达 CCR2,但这并不包括那些产生 pDC 的祖细胞。基于这些结果,我们提出 CCR2 参与 pDC 稳态,但其配体 CCL2 不起主要作用。