Fucosyltransferase VII-positive, skin-homing T cells in the blood and skin lesions of atopic dermatitis patients.
Patients with atopic dermatitis (AD) have an abnormally increased frequency of cutaneous lymphocyte antigen (CLA)+ Th2 cells responsible for local inflammation; however, this is paradoxical, given the well-recognized defective capacity of Th2 cells to migrate to the skin sites of inflammation. These discrepant observations would stem from the ambiguity of CLA+ T cells, because CLA does not represent the epitope required for binding to E-selectin but the epitope generated by fucosyltransferase VII (Fuc-TVII) and because skin-homing T cells are composed of three distinct subpopulations; Fuc-TVII+ E-selectin ligand (ESL)+ CLA-, Fuc-TVII+ ESL+ CLA+ and Fuc-TVII- ESL- CLA+ cells. We therefore asked which subpopulations of skin-homing Th2 cells could be increased in the blood and skin lesions of AD. We analysed the frequencies of the three subpopulations in purified CD4+ peripheral blood T cells from AD patients and healthy controls by immunohistochemistry and flow cytometry. The Fuc-TVII+ CLA+ or CLA+ ESL+ CCR4+ cells were dramatically increased in frequency not only in the blood but also in the skin lesions of AD patients and this increase was related to the severity of the clinical symptoms. Our data indicate the clinical importance of identifying skin-homing T cells with the potent capacity to migrate into the skin by analysing their Fuc-TVII expression and E-selectin binding ability in patients with AD.
Mizukawa
Yoshiko
Y
Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan. ymizu@kyorin-u.ac.jp
Takahashi
Ryo
R
Yamazaki
Yoshimi
Y
Kimishima
Momoko
M
Shiohara
Tetsuo
T
D000328:Adult; D000704:Analysis of Variance; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism; D019040:E-Selectin / Q000276:immunology; D005434:Flow Cytometry; D005647:Fucosyltransferases / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism; D011565:Psoriasis / Q000276:immunology / Q000378:metabolism; D054398:Receptors, CCR4 / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000032:analysis; D012867:Skin / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C515354:CCR4 protein, human; D017252:CD3 Complex; C063419:CTAGE1 protein, human; D019040:E-Selectin; D008024:Ligands; D008562:Membrane Glycoproteins; D054398:Receptors, CCR4; D016201:Receptors, Lymphocyte Homing; C502597:FUT7 protein, human; D005647:Fucosyltransferases