Immunity
Volume 45, Issue 2, 16 August 2016, Pages 305-318
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Article
Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery

https://doi.org/10.1016/j.immuni.2016.07.019Get rights and content
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Highlights

  • Thymic XCR1+ DCs undergo a high maturation rate essential for central tolerance

  • Thymic DCs express genes preventing establishment of tolerance against viruses

  • Thymic and peripheral tolerogenic DC maturation involves identical molecular changes

  • Tolerogenic DC maturation results in changes as complex as immunogenic DC maturation

Summary

Dendritic cells (DCs) are instrumental in the initiation of 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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