Dendritic Cell Migration Toward CCL21 Gradient Requires Functional Cx43

Article Article scientifique Article Dendritic Cell Migration Toward CCL21 Gradient Requires Functional Cx43 eng 2018 author Ruez Richard 769457 author Dubrot Armendariz Juan 744966 author Zoso Alice 827165 author Bacchetta Marc 94948 author Molica Filippo 525132 author Hugues Stéphanie 663452 author Kwak Brenda 113350 author Chanson Marc 0000-0001-8104-2090 32865 288 10.3389/fphys.2018.00288 29636699 1664-042X https://www.frontiersin.org/articles/10.3389/fphys.2018.00288/full Dendritic cells (DCs) travel through lymphatic vessels to transport antigens and present them to T cells in lymph nodes. DCs move directionally toward lymphatics by virtue of their CCR7 and a CCL21 chemotactic gradient. We evaluated in vivo and in bone marrow-derived dendritic cells (BMDCs) whether the gap junction protein Cx43 contributes to CCL21/CCR7-dependent DC migration in wild-type (WT) mice, heterozygous (Cx43+/-) mice and mice expressing a truncated form of Cx43 lacking its regulatory C-terminus (Cx43K258/-). In a model of flank skin inflammation, we found that the recruitment of myeloid DCs (mDCs) to skin draining lymph nodes was reduced in Cx43K258/- mice as compared to WT and Cx43+/- mice. In addition, the migration of Cx43K258/- BMDCs toward CCL21 was abolished in an in vitro chemotactic assay while it was only reduced in Cx43+/- cells. Both mutant genotypes showed defects in the directionality of BMDC migration as compared to WT BMDCs. No difference was found between the three populations of BMDCs in terms of expression of surface markers (CD11c, CD86, CD80, CD40, MHC-II, and CCR7) after differentiation and TLR activation. Finally, examination of the CCR7-induced signaling pathways in BMDCs revealed normal receptor-induced mobilization of intracellular Ca2+. These results demonstrate that full expression of an intact Cx43 is critical to the directionality and rate of DC migration, which may be amenable to regulation of the immune response. Dewey 616.07 Dewey 618 Swiss National Science Foundation Host-pathogen interaction and cell-to-cell signaling in the normal and cystic fibrosis airway epithelium 134907 CH Project funding 137 Département de pathologie et immunologie 21F 58 Département de pédiatrie, gynécologie et obstétrique 223 false 397 Connexines et pathologies cardiovasculaires 665 180 Mucoviscidose et jonctions communicantes 229 563 Pathologie et immunologie 906 Frontiers in Physiology 9 a5f8ce81-0848-48b5-9def-d8f96fb9fc2d Article (Published version) Public Ruez_fphys-09-00288.pdf 2354963 application/pdf OA OTHER openAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique

Title	Published in	Year	Views	Downloads

Dendritic Cell Migration Toward CCL21 Gradient Requires Functional Cx43	Frontiers in Physiology	2018	573	315
Connexins in respiratory and gastrointestinal mucosal immunity	FEBS letters	2014	678	1

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Ruez, Richard