⍺4β7 Integrin is essential for contact hypersensitivity by regulating migration of T cells to skin - 07/08/11
, Makoto Sugaya, MD, PhD a, Manabu Tomita, MD, PhD a, Hiromichi Kai, MD a, Tomomitsu Miyagaki, MD, PhD a, Hidehisa Saeki, MD, PhD a, Kunihiko Tamaki, MD, PhD a, Douglas A. Steeber, PhD b, Thomas F. Tedder, PhD c, Shinichi Sato, MD, PhD a
Reprint requests: Takafumi Kadono, MD, PhD, Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.Abstract |
Background |
β7 Integrin, a cell adhesion molecule, is present in the form of ⍺4β7 integrin or ⍺Eβ7 integrin. ⍺4β7 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 ⍺4β7 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 ⍺E integrin–deficient mice.
Results |
β7 Integrin–deficient mice, not ⍺E 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–⍺4β7 integrin neutralizing antibody elicit impaired contact hypersensitivity responses.
Conclusion |
⍺4β7 Integrin contributes to contact hypersensitivity responses by regulating T-cell migration to inflammatory skin.
Le texte complet de cet article est disponible en PDF.Key words : ⍺4β7 Integrin, contact hypersensitivity responses, VCAM-1
Abbreviations used : ⍺E−/−, APC, β7−/−, CFSE, CHS, CLA, DC, DLN, DNBS, DNFB, FACS, FITC, MAdCAM-1, oxazolone, VCAM-1, WT
Plan
| Supported by grants from the Ministry of Education, Culture, Sports and Technology in Japan. |
|
| Disclosure of potential conflict of interest: H. Ohmatsu has received research support from the Ministry of Education, Culture, Sports and Technology in Japan. The rest of the authors have declared that they have no conflict of interest. |
Vol 126 - N° 6
P. 1267-1276 - décembre 2010 Retour au numéro
Article précédent
- Human basophils express amphiregulin in response to T cell–derived IL-3
- Yilin Qi, Darwin J. Operario, Christopher M. Oberholzer, James J. Kobie, R. John Looney, Steve N. Georas, Tim R. Mosmann
- Expression of functional receptor activity modifying protein 1 by airway epithelial cells with dysregulation in asthma
- Kandace Bonner, Harsha H. Kariyawasam, F. Runa Ali, Peter Clark, A. Barry Kay
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?