α4β7 Integrin is essential for contact hypersensitivity by regulating migration of T cells to skin.
BACKGROUND
β7 Integrin, a cell adhesion molecule, is present in the form of α4β7 integrin or αEβ7 integrin. α4β7 Integrin is expressed on most leucocytes and is essential for their migration to gut-associated lymphoid tissues by interacting with its primary ligand, mucosal addressin cell adhesion molecule-1, which is preferentially expressed in gut-associated lymphoid tissues. Although the importance of α4β7 integrin in intestinal inflammation has been established, its role in cutaneous inflammation remains to be elucidated.


OBJECTIVE
We sought to investigate the role of β7 integrin in cutaneous inflammation.


METHODS
We used a murine contact hypersensitivity model and examined the role of β7 integrin by using β7 integrin-deficient and αE integrin-deficient mice.


RESULTS
β7 Integrin-deficient mice, not αE integrin-deficient mice, are defective in contact hypersensitivity responses. β7 Integrin deficiency does not affect irritant contact dermatitis. The distribution, migration, and function of antigen presenting cells from β7 integrin-deficient mice are comparable to those from wild-type mice. Moreover, sensitized β7 integrin-deficient T cells are able to respond to antigen stimuli in vitro and elicit contact hypersensitivity responses when directly injected into the skin. However, they are defective in reaching the skin under inflammatory conditions, resulting in reduced contact hypersensitivity responses when intravenously injected. Furthermore, intraperitoneal injection of anti-α4β7 integrin neutralizing antibody elicit impaired contact hypersensitivity responses.


CONCLUSIONS
α4β7 Integrin contributes to contact hypersensitivity responses by regulating T-cell migration to inflammatory skin.
Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Hanako
H
Ohmatsu
Takafumi
T
Kadono
Makoto
M
Sugaya
Manabu
M
Tomita
Hiromichi
H
Kai
Tomomitsu
T
Miyagaki
Hidehisa
H
Saeki
Kunihiko
K
Tamaki
Douglas A
DA
Steeber
Thomas F
TF
Tedder
Shinichi
S
Sato
D019264:Adoptive Transfer; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D003877:Dermatitis, Contact / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D018928:Immunity, Mucosal / Q000187:drug effects; D016023:Integrins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012867:Skin / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D019138:Antibodies, Blocking; D016023:Integrins; C071777:integrin alpha4beta7; C070709:integrin alphaEbeta7