Thymic XCR1+ dendritic cells undergo a functional maturation fundamentally similar to that of peripheral tolerogenic XCR1+ dendritic cells

Dendritic cells (DC) play critical roles in central and peripheral T cell tolerance. DC found in the steady-state periphery undergo an homeostatic, tolerogenic, maturation that promotes interaction with naive T cells and induction of abortive responses. In contrast, thymic DC are thought to exist solely in an immature state. In this study, we show that XCR1+ thymic DC constitutively mature into a stage characterized by high levels of molecules involved in T cell activation. This unanticipated mature stage corresponded to a third of the XCR1+ thymic DC and fully accounted for their ability to cross-present self-antigens to developing T cells. Transcriptomic analysis of the XCR1+ DC found in thymus and steady-state periphery revealed that their maturation involves profound and convergent changes. Unexpectedly, maturation resulted in down-regulation of genes conferring their specific function on XCR1+ DC. Paradoxically, upon maturation, central and peripheral tolerogenic XCR1+ DC up-regulated many genes thought to drive pro-inflammatory T-cell responses. Thus, our results reveal that thymic XCR1+ DC undergo constitutive maturation and emphasize the common mechanisms operating for both central and peripheral tolerance induction by XCR1+ DC.

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Ardouin L, Luche H, Chelbi R, Carpentier S, Shawket A, Montanana Sanchis F, Santa Maria C, Grenot P, Alexandre Y, Grégoire C, Fries A, Vu Manh TP, Tamoutounour S, Crozat K, Tomasello E, Jorquera A, Fossum E, Bogen B, Azukizawa H, Bajenoff M, Henri S, Dalod M, Malissen B