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J Exp Med ; 218(7)2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-33988714

RESUMO

Dendritic cell (DC) migration to draining lymph nodes (dLNs) is a slow process that is believed to begin with DCs approaching and entering into afferent lymphatic capillaries. From capillaries, DCs slowly crawl into lymphatic collectors, where lymph flow induced by collector contraction supports DC detachment and thereafter rapid, passive transport to dLNs. Performing a transcriptomics analysis of dermal endothelial cells, we found that inflammation induces the degradation of the basement membrane (BM) surrounding lymphatic collectors and preferential up-regulation of the DC trafficking molecule VCAM-1 in collectors. In crawl-in experiments performed in ear skin explants, DCs entered collectors in a CCR7- and ß1 integrin-dependent manner. In vivo, loss of ß1-integrins in DCs or of VCAM-1 in lymphatic collectors had the greatest impact on DC migration to dLNs at early time points when migration kinetics favor the accumulation of rapidly migrating collector DCs rather than slower capillary DCs. Taken together, our findings identify collector entry as a critical mechanism enabling rapid DC migration to dLNs in inflammation.


Assuntos
Movimento Celular/fisiologia , Células Dendríticas/metabolismo , Células Endoteliais/metabolismo , Inflamação/metabolismo , Linfonodos/metabolismo , Vasos Linfáticos/metabolismo , Regulação para Cima/fisiologia , Molécula 1 de Adesão de Célula Vascular/metabolismo , Animais , Membrana Basal/metabolismo , Membrana Basal/fisiopatologia , Células Dendríticas/fisiologia , Células Endoteliais/fisiologia , Feminino , Humanos , Inflamação/fisiopatologia , Integrina beta1/metabolismo , Linfonodos/fisiopatologia , Vasos Linfáticos/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Receptores CCR7/metabolismo , Pele/metabolismo , Pele/fisiopatologia , Ativação Transcricional/fisiologia
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