Formation of the Intrathymic Dendritic Cell Pool Requires CCL21-Mediated Recruitment of CCR7(+) Progenitors to the Thymus.
Formation of the Intrathymic Dendritic Cell Pool Requires CCL21-Mediated Recruitment of CCR7(+) Progenitors to the Thymus.
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DOI：
10.4049/jimmunol.1800348
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发表时间：
2018-07-15
期刊：
影响因子：
--
通讯作者：
Anderson G
中科院分区：
文献类型：
--
作者：
Cosway EJ;Ohigashi I;Schauble K;Parnell SM;Jenkinson WE;Luther S;Takahama Y;Anderson G
在胸腺中的αβ T细胞发育期间，新选择的CD 4+和CD 8+胸腺细胞迁移到髓质区域使得耐受机制能够清除新选择的自身反应特异性αβ TCR库。胸腺树突状细胞（DC）在这一过程中起着关键作用，并由三个不同的亚群组成，它们的发育起源不同。因此，浆细胞样DC和Sirpα+常规DC 2型是胸腺外来源的，并通过各自表达趋化因子受体CCR 9和CCR 2进入胸腺。相反，虽然已知Sirpα−常规DC 1型（cDC 1）在胸腺内由未成熟的祖细胞产生，但这种胸腺定殖祖细胞的确切性质以及控制其进入胸腺的机制尚不清楚。在这篇文章中，我们报告了选择性减少胸腺cDC 1缺乏趋化因子受体CCR 7的小鼠。此外，我们发现胸腺含有表达CCR 7的CD 11 c +MHC II类−Sirpα− Flt 3 + cDC祖细胞群，并且这些细胞向胸腺的迁移在Ccr 7 −/−小鼠中受损。此外，Ccr 7-/-小鼠中的胸腺cDC 1缺陷也反映在plt/plt小鼠中，对单独缺乏CCR 7配体CCL 21 Ser（Ccl 21 a-/-）或CCL 19（Ccl 19-/-）的小鼠的进一步分析表明，CCR 7-CCL 21 Ser在胸腺内cDC 1发育过程中发挥着重要作用。总的来说，我们的数据支持CCR 7-CCL 21 Ser相互作用引导cDC祖细胞迁移到胸腺以正确形成胸腺内cDC 1库的机制。
During αβ T cell development in the thymus, migration of newly selected CD4+ and CD8+ thymocytes into medullary areas enables tolerance mechanisms to purge the newly selected αβ TCR repertoire of autoreactive specificities. Thymic dendritic cells (DC) play key roles in this process and consist of three distinct subsets that differ in their developmental origins. Thus, plasmacytoid DC and Sirpα+ conventional DC type 2 are extrathymically derived and enter into the thymus via their respective expression of the chemokine receptors CCR9 and CCR2. In contrast, although Sirpα− conventional DC type 1 (cDC1) are known to arise intrathymically from immature progenitors, the precise nature of such thymus-colonizing progenitors and the mechanisms controlling their thymus entry are unclear. In this article, we report a selective reduction in thymic cDC1 in mice lacking the chemokine receptor CCR7. In addition, we show that the thymus contains a CD11c+MHC class II−Sirpα−Flt3+ cDC progenitor population that expresses CCR7, and that migration of these cells to the thymus is impaired in Ccr7−/− mice. Moreover, thymic cDC1 defects in Ccr7−/− mice are mirrored in plt/plt mice, with further analysis of mice individually lacking the CCR7 ligands CCL21Ser (Ccl21a−/−) or CCL19 (Ccl19−/−) demonstrating an essential role for CCR7-CCL21Ser during intrathymic cDC1 development. Collectively, our data support a mechanism in which CCR7-CCL21Ser interactions guide the migration of cDC progenitors to the thymus for correct formation of the intrathymic cDC1 pool.
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影响因子：
64.8
作者：
ARDAVIN, C;WU, L;SHORTMAN, K
通讯作者：
SHORTMAN, K
影响因子：
5.4
作者：
Hadeiba, Husein;Butcher, Eugene C.
通讯作者：
Butcher, Eugene C.
DOI：
10.1084/jem.20041457
发表时间：
2004-10-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gallegos AM;Bevan MJ
通讯作者：
Bevan MJ
影响因子：
32.4
作者：
Hadeiba H;Lahl K;Edalati A;Oderup C;Habtezion A;Pachynski R;Nguyen L;Ghodsi A;Adler S;Butcher EC
通讯作者：
Butcher EC
影响因子：
64.5
作者：
Förster, R;Schubel, A;Lipp, M
通讯作者：
Lipp, M