期刊
IMMUNITY
卷 45, 期 2, 页码 305-318出版社
CELL PRESS
DOI: 10.1016/j.immuni.2016.07.019
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类别
资金
- CNRS
- INSERM
- PHENOMIN
- European Research Council [281225, 322465]
- DCBiol Labex [ANR-11-LA-BEX-0043, ANR-10-IDEX-0001-02]
- A*MIDEX project [ANR-11-IDEX-0001-02]
- I2HD CIML-SANOFI project
- SYB-ILLA European collaborative project
- [ANR-11-DPBS-002]
- European Research Council (ERC) [322465, 281225] Funding Source: European Research Council (ERC)
Dendritic cells (DCs) are instrumental in the initiationof T cell responses, but how thymic and peripheral tolerogenic DCs differ globally from Toll-like receptor (TLR)-induced immunogenic DCs remains unclear. Here, we show that thymic XCR1(+) DCs undergo a high rate of maturation, accompanied by profound gene-expression changes that are essential for central tolerance and also happen in germ-free mice. Those changes largely overlap those occurring during tolerogenic and, more unexpectedly, TLR-induced maturation of peripheral XCR1(+) DCs, arguing against the commonly held view that tolerogenic DCs undergo incomplete maturation. Interferon-stimulated gene (ISG) expression was among the few discriminators of immunogenic and tolerogenic XCR1(+) DCs. Tolerogenic XCR1(+) thymic DCs were, however, unique in expressing ISGs known to restrain virus replication. Therefore, a broad functional convergence characterizes tolerogenic and immunogenic XCR1(+) DC maturation in the thymus and periphery, maximizing antigen presentation and signal delivery to developing and to conventional and regulatory mature T cells.
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