CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions.
The CC chemokine receptor CCR7 has been identified as a key regulator of homeostatic B and T cell trafficking to secondary lymphoid organs. Data presented here demonstrate that CCR7 is also an essential mediator for entry of both dermal and epidermal dendritic cells (DC) into the lymphatic vessels within the dermis while this receptor is dispensable for the mobilization of Langerhans cells from the epidermis to the dermis. Moreover, a distinct population of CD11c(+)MHCII(high) DC showing low expression of the costimulatory molecules CD40, CD80, and CD86 in wild-type animals was virtually absent in skin-draining lymph nodes of CCR7-deficient mice under steady-state conditions. We provide evidence that these cells represent a semimature population of DC that is capable of initiating T cell proliferation under conditions known to induce tolerance. Thus, our data identify CCR7 as a key regulator that governs trafficking of skin DC under both inflammatory and steady-state conditions.
Ohl
Lars
L
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany.
Mohaupt
Mariette
M
Czeloth
Niklas
N
Hintzen
Gabriele
G
Kiafard
Ziba
Z
Zwirner
Jörg
J
Blankenstein
Thomas
T
Henning
Golo
G
Förster
Reinhold
R
D000818:Animals; D039521:CD11c Antigen / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D002465:Cell Movement / Q000276:immunology / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
D039521:CD11c Antigen; C515371:Ccr7 protein, mouse; D000949:Histocompatibility Antigens Class II; D054400:Receptors, CCR7; D019707:Receptors, Chemokine