Hassall's corpuscles with cellular-senescence features maintain IFNα production through neutrophils and pDC activation in the thymus.
Hassall's corpuscles with cellular-senescence features maintain IFNα production through neutrophils and pDC activation in the thymus.
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DOI：
10.1093/intimm/dxy073
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发表时间：
2019-03-05
影响因子：
4.4
通讯作者：
Hamazaki, Yoko
中科院分区：
文献类型：
--
作者：
Wang, Jianwei;Sekai, Miho;Matsui, Takeshi;Fujii, Yosuke;Matsumoto, Mitsuru;Takeuchi, Osamu;Minato, Nagahiro;Hamazaki, Yoko
哈塞尔小体（Hassall's corpuscles，HC）由角化的、终末分化的胸腺髓质上皮细胞（mTEC）组成，其在Aire的控制下发育。在这里，我们证明了HC-mTECs显示细胞衰老的特征，并产生炎性细胞因子和趋化因子，包括CXCL 5，从而招募和激活中性粒细胞在胸腺髓质中产生IL-23。我们进一步表明，表达IL-23受体的胸腺浆细胞样树突状细胞（pDC）组成型产生Ifna，Ifna以IL-23 α依赖性方式在单阳性（SP）细胞成熟中发挥作用。用抗Ly 6 G抗体注射的中性粒细胞消耗导致胸腺pDC中Ifna表达的显著降低，表明胸腺中性粒细胞活化是稳态条件下胸腺pDC中Ifna表达的基础。显示HC增生的新西兰白色小鼠品系表现出比B6小鼠更多的胸腺中性粒细胞和pDC的数量和活化，而具有缺陷HC发育和SP胸腺细胞成熟的Aire缺陷B6小鼠显示这些细胞的数量和活化显著受损。这些结果共同表明，具有细胞衰老特征的HC-mTEC启动了独特的细胞活化级联反应，包括中性粒细胞和pDC，导致胸腺髓质中SP T细胞成熟所需的组成型IFNα表达。
Hassall’s corpuscles activate neutrophils to stimulate pDCs in the thymus Hassall’s corpuscles (HCs) are composed of cornifying, terminally differentiated medullary thymic epithelial cells (mTECs) that are developed under the control of Aire. Here, we demonstrated that HC-mTECs show features of cellular senescence and produce inflammatory cytokines and chemokines including CXCL5, thereby recruiting and activating neutrophils to produce IL-23 in the thymic medulla. We further indicated that thymic plasmacytoid dendritic cells (pDCs) expressing IL-23 receptors constitutively produced Ifna, which plays a role in single positive (SP) cell maturation, in an Il23a-dependent manner. Neutrophil depletion with anti-Ly6G antibody injection resulted in a significant decrease of Ifna expression in the thymic pDCs, suggesting that thymic neutrophil activation underlies the Ifna expression in thymic pDCs in steady state conditions. A New Zealand White mouse strain showing HC hyperplasia exhibited greater numbers and activation of thymic neutrophils and pDCs than B6 mice, whereas Aire-deficient B6 mice with defective HC development and SP thymocyte maturation showed significantly compromised numbers and activation of these cells. These results collectively suggested that HC-mTECs with cell-senescence features initiate a unique cell activation cascade including neutrophils and pDCs leading to the constitutive IFNα expression required for SP T-cell maturation in the thymic medulla.
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DOI：
10.4049/jimmunol.0804133
发表时间：
2009-12-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Laan M;Kisand K;Kont V;Möll K;Tserel L;Scott HS;Peterson P
通讯作者：
Peterson P
DOI：
10.1126/science.1218004
发表时间：
2012-04-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Dudakov JA;Hanash AM;Jenq RR;Young LF;Ghosh A;Singer NV;West ML;Smith OM;Holland AM;Tsai JJ;Boyd RL;van den Brink MR
通讯作者：
van den Brink MR
DOI：
10.1111/nyas.12960
发表时间：
2015-01-01
期刊：
YEAR IN IMMUNOLOGY
影响因子：
--
作者：
Chan, Alice Y.;Anderson, Mark S.
通讯作者：
Anderson, Mark S.
影响因子：
10.5
作者：
Chien, Yuchen;Scuoppo, Claudio;Lowe, Scott W.
通讯作者：
Lowe, Scott W.
影响因子：
29.4
作者：
Dobes, Jan;Neuwirth, Ales;Filipp, Dominik
通讯作者：
Filipp, Dominik