alpha 4 beta 7 Integrin is essential for contact hypersensitivity by regulating migration of T cells to skin

作者:Ohmatsu Hanako; Kadono Takafumi*; Sugaya Makoto; Tomita Manabu; Kai Hiromichi; Miyagaki Tomomitsu; Saeki Hidehisa; Tamaki Kunihiko; Steeber Douglas A; Tedder Thomas F; Sato Shinichi
来源:Journal of Allergy and Clinical Immunology, 2010, 126(6): 1267-1276.
DOI:10.1016/j.jaci.2010.08.048

摘要

Background: beta 7 Integrin, a cell adhesion molecule, is present in the form of alpha 4 beta 7 integrin or alpha E beta 7 integrin. alpha 4 beta 7 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 alpha 4 beta 7 integrin in intestinal inflammation has been established, its role in cutaneous inflammation remains to be elucidated.
Objective: We sought to investigate the role of beta 7 integrin in cutaneous inflammation.
Methods: We used a murine contact hypersensitivity model and examined the role of beta 7 integrin by using beta 7 integrin-deficient and alpha E integrin-deficient mice.
Results: beta 7 Integrin-deficient mice, not aE integrin-deficient mice, are defective in contact hypersensitivity responses. beta 7 Integrin deficiency does not affect irritant contact dermatitis. The distribution, migration, and function of antigen presenting cells from beta 7 integrin-deficient mice are comparable to those from wild-type mice. Moreover, sensitized beta 7 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-alpha 4 beta 7 integrin neutralizing antibody elicit impaired contact hypersensitivity responses.
Conclusion: alpha 4 beta 7 Integrin contributes to contact hypersensitivity responses by regulating T-cell migration to inflammatory skin. (J Allergy Clin Immunol 2010;126:1267-76.)

  • 出版日期2010-12