Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery

Laurence Ardouin; Hervé Luche; Rabie Chelbi; Sabrina Carpentier; Alaa Shawket; Frédéric Montañana-Sanchis; Camille Santa Maria; Pierre Grenot; Yannick Alexandre; Claude Grégoire; Anissa Fries; Thien-Phong Vu Manh; Samira Tamoutounour; Karine Crozat; Elena Tomasello; Audrey Jorquera; Even Fossum; Bjarne Bogen; Hiroaki Azukizawa; Marc Bajenoff; Sandrine Henri; Marc Dalod; Bernard Malissen

doi:10.1016/j.immuni.2016.07.019

Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery

Laurence Ardouin ¹ Hervé Luche ^{1, 2} Rabie Chelbi ¹ Sabrina Carpentier ³ Alaa Shawket ¹ Frédéric Montañana-Sanchis ¹ Camille Santa Maria ² Pierre Grenot ² Yannick Alexandre ^{1, 4} Claude Grégoire ¹ Anissa Fries ¹ Thien-Phong Vu Manh ¹ Samira Tamoutounour ¹ Karine Crozat ¹ Elena Tomasello ¹ Audrey Jorquera ¹ Even Fossum ⁵ Bjarne Bogen ⁵ Hiroaki Azukizawa ⁶ Marc Bajenoff ¹ Sandrine Henri ¹ Marc Dalod ^{1, *} Bernard Malissen ^{2, 1, *}

* Auteur correspondant

1 CIML - Centre d'Immunologie de Marseille - Luminy

2 CIPHE - Centre d'Immunophénomique

3 Mi-mAbs (C/O CIML)

CIML - Centre d'Immunologie de Marseille - Luminy

4 VIM - Unité de recherche Virologie et Immunologie Moléculaires

5 Center for Immune Regulation - University of Oslo & Oslo University Hospital Rikshospitalet

6 Department of Dermatology [Osaka, Japan]

Abstract : 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.

Type de document :

Article dans une revue

Immunity, Elsevier, 2016, 45 ((2)), pp.305-18. 〈10.1016/j.immuni.2016.07.019〉

Domaine :

Sciences du Vivant [q-bio] / Immunologie

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http://www.hal.inserm.fr/inserm-01374574
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Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery

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Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery

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