Thymic stromal lymphopoietin-activated plasmacytoid dendritic cells induce the generation of FOXP3+ regulatory T cells in human thymus.
Thymic stromal lymphopoietin-activated plasmacytoid dendritic cells induce the generation of FOXP3+ regulatory T cells in human thymus.
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DOI：
10.4049/jimmunol.0804106
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发表时间：
2010-03-15
期刊：
影响因子：
--
通讯作者：
Liu YJ
中科院分区：
文献类型：
--
作者：
Hanabuchi S;Ito T;Park WR;Watanabe N;Shaw JL;Roman E;Arima K;Wang YH;Voo KS;Cao W;Liu YJ
人胸腺含有主要的树突状细胞（DC）亚群、髓样DC（mDC）和浆细胞样DC（pDC）。我们之前的研究表明，mDC在哈萨尔小体上皮细胞产生的胸腺基质淋巴细胞生成素（TSLP）的作用下，诱导CD 4 + CD 25 −胸腺细胞分化为人类胸腺髓质内的叉头盒P3+（FOXP 3+）调节性T细胞（TR）。在这项研究中，我们表明，pDC表达TSLP受体和IL-7受体α复合物激活后，成为响应TSLP。TSLP激活的人pDC分泌巨噬细胞衍生的趋化因子CCL-22和胸腺和激活调节的趋化因子CCL-17，但不分泌Th 1或Th 2极化细胞因子。TSLP激活的pDCs诱导CD 4 + CD 8 − CD 25 −胸腺细胞产生FOXP 3 + TR，这可以被Th 1极化细胞因子IL-12或Th 2极化细胞因子IL-4强烈抑制。有趣的是，由TSLP-pDC诱导的FOXP 3 + TR比由TSLP-mDC诱导的表达更多的IL-10但更少的TGF-β。这些数据表明，胸腺上皮细胞表达的TSLP可以激活mDC和pDC，以在人胸腺中正向选择具有不同细胞因子产生潜力的FOXP 3 + TR。TSLP不能诱导DC成熟而不产生Th 1或Th 2极化细胞因子，这可能为TR的发展提供了胸腺小生境。
Human thymus contains major dendritic cell (DC) subsets, myeloid DCs (mDCs), and plasmacytoid DCs (pDCs). We previously showed that mDCs, educated by thymic stromal lymphopoietin (TSLP) produced by the epithelial cells of the Hassall’s corpuscles, induced differentiation of CD4+CD25− thymocytes into Forkhead Box P3+ (FOXP3+) regulatory T cells (TR) within the medulla of human thymus. In this study, we show that pDCs expressed the TSLP receptor and IL-7 receptor a complexes upon activation and became responsive to TSLP. TSLP-activated human pDCs secrete macrophage-derived chemokine CCL-22 and thymus- and activation-regulated chemokine CCL-17 but not Th1- or Th2-polarizing cytokines. TSLP-activated pDCs induced the generation of FOXP3+ TR from CD4+CD8−CD25− thymocytes, which could be strongly inhibited by Th1-polarizing cytokine IL-12 or Th2-polarizing cytokine IL-4. Interestingly, the FOXP3+ TR induced by the TSLP-pDCs expressed more IL-10 but less TGF-b than that induced by the TSLP-mDCs. These data suggest that TSLP expressed by thymic epithelial cells can activate mDCs and pDCs to positively select the FOXP3+ TR with different cytokine production potential in human thymus. The inability of TSLP to induce DC maturation without producing Th1- or Th2-polarizing cytokines may provide a thymic niche for TR development.
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影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
30.5
作者：
Aschenbrenner, Katharina;D'Cruz, Louise M.;Klein, Ludger
通讯作者：
Klein, Ludger
影响因子：
15.9
作者：
Bendriss-Vermare, N;Barthélémy, C;Brière, F
通讯作者：
Brière, F
影响因子：
20.3
作者：
Ito, T;Kanzler, H;Liu, YJ
通讯作者：
Liu, YJ
DOI：
10.1084/jem.20050784
发表时间：
2005-10-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fontenot JD;Dooley JL;Farr AG;Rudensky AY
通讯作者：
Rudensky AY