Distinct antigen trafficking from skin in the steady and active states.
In antigen trafficking from the skin, it has been postulated that Langerhans cells/dendritic cells are activated after capturing exogenous antigens, up-regulate the expression of the chemokine receptor, CCR7, and migrate into lymphoid organs in response to the signaling of a chemokine, CCL21, which is expressed in lymphatic vessels and T cell zone stromal cells. Here we demonstrate that there is a distinct pathway of antigen trafficking from skin in the steady state that is independent of CCL21-CCR7 signaling. Employing melanin granules as an endogenous traceable antigen, we developed a system for visualizing antigen trafficking using mice with melanocytosis in the skin. We found the abrogation of antigen trafficking into regional lymph nodes (LN) in CCL21-Ser-deficient paucity of lymph node T cells (plt) mice in the active state induced by lipopolysaccharide injection, corresponding with previous reports, but normal accumulation of antigen in regional LN under steady-state conditions. These findings suggest that self-antigen is trafficking constitutively using pathway(s) other than that of the active state and the constitutive trafficking might regulate self-reactivity of the immune system.
Division of Immunology, Department of Molecular and Cellular Biology, School of Life Science, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan. myoshi@grape.med.tottori-u.ac.jp
Miya
M
Yoshino
Hidetoshi
H
Yamazaki
Hideki
H
Nakano
Terutaka
T
Kakiuchi
Kazuo
K
Ryoke
Takahiro
T
Kunisada
Shin-Ichi
S
Hayashi
D000818:Animals; D000941:Antigens / Q000276:immunology; D002465:Cell Movement / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007801:Langerhans Cells / Q000502:physiology*; D008198:Lymph Nodes / Q000276:immunology; D008543:Melanins / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism*; D012867:Skin / Q000276:immunology; D012871:Skin Diseases / Q000235:genetics / Q000276:immunology; D019089:Stem Cell Factor / Q000235:genetics; D019076:Transgenes / Q000276:immunology
D000941:Antigens; C515370:CCR7 protein, human; C515371:Ccr7 protein, mouse; D008543:Melanins; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D019089:Stem Cell Factor