Osteopontin is involved in the initiation of cutaneous contact hypersensitivity by inducing Langerhans and dendritic cell migration to lymph nodes.
Osteopontin (OPN) is a chemotactic protein that attracts immune cells, to inflammatory sites. The sensitization phase of allergic cutaneous contact hypersensitivity (CHS) requires the migration of Langerhans cells/dendritic cells (LCs/DCs) from skin to draining lymph nodes. Characterizing OPN function for LC/DC migration we found upregulated OPN expression in hapten sensitized skin and draining lymph nodes. OPN induces chemotactic LC/DC migration, initiates their emigration from the epidermis, and attracts LCs/DCs to draining lymph nodes by interacting with CD44 and alphav integrin. Furthermore, OPN-deficient mice have a significantly reduced CHS response that correlates with an impaired ability of OPN-deficient mice to attract LCs/DCs to draining lymph nodes. In conclusion, OPN is an important factor in the initiation of CHS by guiding LCs/DCs from skin into lymphatic organs.
Weiss
J M
JM
Department of Dermatology, University of Freiburg, D-79104 Freiburg, Germany. weiss@haut.ukl.uni-freiburg.de
Renkl
A C
AC
Maier
C S
CS
Kimmig
M
M
Liaw
L
L
Ahrens
T
T
Kon
S
S
Maeda
M
M
Hotta
H
H
Uede
T
T
Simon
J C
JC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D002454:Cell Differentiation; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D002633:Chemotaxis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D004195:Disease Models, Animal; D004817:Epidermis / Q000276:immunology; D018960:Hyaluronan Receptors / Q000276:immunology; D007271:Injections, Intradermal; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053495:Osteopontin; D019030:Receptors, Vitronectin / Q000096:biosynthesis / Q000276:immunology; D012795:Sialoglycoproteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D018960:Hyaluronan Receptors; D019030:Receptors, Vitronectin; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin