CCR7 Modulates the Generation of Thymic Regulatory T Cells by Altering the Composition of the Thymic Dendritic Cell Compartment.
CCR7 Modulates the Generation of Thymic Regulatory T Cells by Altering the Composition of the Thymic Dendritic Cell Compartment.
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DOI：
10.1016/j.celrep.2017.09.016
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发表时间：
2017-10-03
期刊：
影响因子：
8.8
通讯作者：
Ehrlich LIR
中科院分区：
文献类型：
--
作者：
Hu Z;Li Y;Van Nieuwenhuijze A;Selden HJ;Jarrett AM;Sorace AG;Yankeelov TE;Liston A;Ehrlich LIR
Upon recognition of auto-antigens, thymocytes are negatively selected or diverted to a regulatory T cell (Treg) fate. CCR7 is required for negative selection of auto-reactive thymocytes in the thymic medulla. Here we describe an unanticipated contribution of CCR7 to intrathymic Treg generation. Ccr7−/− mice have increased Treg cellularity, due to a hematopoietic, but non-T cell autonomous CCR7 function. CCR7 expression by thymic dendritic cells (DC) promotes survival of mature Sirpα− DC. Thus, CCR7 deficiency results in apoptosis of Sirpα− DC, which is counterbalanced by expansion of immature Sirpα+ DC, which efficiently induce Treg generation. CCR7 deficiency results in enhanced intrathymic generation of Treg at the neonatal stage and in lymphopenic adults, when Treg differentiation is critical for establishing self-tolerance. Together these results reveal a complex function for CCR7 in thymic tolerance induction, in which CCR7 not only promotes negative selection, but also governs intrathymic Treg generation via non-thymocyte intrinsic mechanisms. CCR7 promotes thymocyte medullary entry and is thus required for negative selection. Hu et al. show that CCR7 also regulates intrathymic generation of regulatory T cells (Treg) through a non-T cell intrinsic mechanism. CCR7 regulates the composition of the thymic conventional DC compartment, which in turn restrains intrathymic Treg generation.
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DOI：
10.1084/jem.20090300
发表时间：
2009-06-08
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Guerau-de-Arellano M;Martinic M;Benoist C;Mathis D
通讯作者：
Mathis D
影响因子：
20.3
作者：
Davalos-Misslitz, Ana C. M.;Worbs, Tim;Foerster, Reinhold
通讯作者：
Foerster, Reinhold
影响因子：
32.4
作者：
Ehrlich, Lauren I. Richie;Oh, David Y.;Lewis, Richard S.
通讯作者：
Lewis, Richard S.
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：
56.9
作者：
Anderson, MS;Venanzi, ES;Mathis, D
通讯作者：
Mathis, D