2002 Fiscal Year Final Research Report Summary
Analysis of Fuc-T VII/CLA expression in skin diseases
| Project/Area Number |
13670900
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | KYORIN UNIVERSITY |
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Principal Investigator |
MIZUKAWA Yoshiko KYORIN UNIVERSITY, DEPARTMENT OF DERMATOLOGY, Assistant, 医学部, 助手 (50301479)
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| Co-Investigator(Kenkyū-buntansha) |
TERAKI Yuichi KYORIN UNIVERSITY, DEPARTMENT OF DERMATOLOGY, Lecturer, 医学部, 講師 (10188667)
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| Project Period (FY) |
2001 – 2002
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| Keywords | fucosyltransferase VII / CLA / lymphocyte / atopic dermatitis |
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| Research Abstract |
Current models generally assume that the increase in circulating CLA^+ T cells observed in atopic dermatitis (AD) patients represents the expansion of skin-homing T cells responsible for local inflammation and tissue damage. However, the increase can be easily explained by altered T cell trafficking. By using a novel mAb for fucosyltransferase VII (Fuc-TVII), we previously established double staining procedures that can accurately identify subpopulations of skin-homing T cells : Fuc-TVII^+ CLA^+, Fuc-TVII^+ CLA^+, and Fuc-TVII^-CLA^+. In this study, we asked which subpopulations were increased in AD patients and whether this increase could have significant implications for immunopathology in the inflammatory sites. In the purified CD4^+ T cells of healthy controls, only about 4% expressed both CLA and Fuc-TVII : this subpopulation was shown to be most avidily bound to E-selectin. The most abundantly identifiable phenotype was Fuc-TVII^-CLA^+ (6%), most of which lost their ability to bind E-selectin. In AD patients, the Fuc-TVII^+ CLA^+ was dramatically increased about three-fold in the frequency (11%) as compared with controls. Next, we asked whether the increased subset could be associated with the generation of ESL (E-selectin ligand) and which chemokine receptors were preferentially expressed on this subset. Surprisingly, while the frequencies of ESL^+CLA^+ Th cells in controls ranged from 4 to 7%, those in AD dramatically increased up to 14%, correlating with the increased frequencies of the Fuc-TVII^+CLA^+ subset The vast majority of this subset was of Th 2 phenotype, because they expressed CCR-4 but not CXCR-3. These results indicate that in AD Th 2 cells accumulate in the circulation despite their ability to migrate into the skin. AD may be a disease of abnormal T cell trafficking in which Th 2 cells fail to traffic efficiently to the skin
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Research Products
(10 results)
