Russo, E. (Erica)

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    T cell migration from inflamed skin to draining lymph nodes requires intralymphatic crawling supported by ICAM-1/LFA-1 interactions
    (Elsevier, 2017) Frei, T. (Thomas); Debes, G.F. (Grudun F.); Proulx, S.T. (Steven T.); Rouzaut, A. (Ana); Hunter, M.C. (Morgan C.); Russo, E. (Erica); Halin, C. (Cornelia); Melero, I. (Ignacio); Coles, M. (Marc); Teijeira, A. (Álvaro); Detmar, M. (Michael)
    T cells are the most abundant cell type found in afferent lymph, but their migration through lymphatic vessels (LVs) remains poorly understood. Performing intravital microscopy in the murine skin, we imaged T cell migration through afferent LVs in vivo. T cells entered into and actively migrated within lymphatic capillaries but were passively transported in contractile collecting vessels. Intralymphatic T cell number and motility were increased during contact-hypersensitivity-induced inflammation and dependent on ICAM-1/LFA-1 interactions. In vitro, blockade of endothelial cell-expressed ICAM-1 reduced T cell adhesion, crawling, and transmigration across lymphatic endothelium and decreased T cell advancement from capillaries into lymphatic collectors in skin explants. In vivo, T cell migration to draining lymph nodes was significantly reduced upon ICAM-1 or LFA-1 blockade. Our findings indicate that T cell migration through LVs occurs in distinct steps and reveal a key role for ICAM-1/LFA-1 interactions in this process.