Expression of Cutaneous Lymphocyte-Associated Antigen Regulated by a Set of Glycosyltransferases in Human T Cells: Involvement of α1,3-Fucosyltransferase VII and β1,4-Galactosyltransferase I
| Autor: | Takuya Tamatani, Takashi Kudo, Hiroko Iwasaki, Fumiaki Nakayama, Tetsuo Shiohara, Yoshiko Mizukawa, Akira Togayachi, Hisashi Narimatsu, Yuichi Teraki, Shoko Nishihara |
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| Rok vydání: | 2000 |
| Předmět: |
Antigens
Differentiation T-Lymphocyte CD4-Positive T-Lymphocytes medicine.medical_treatment T-Lymphocytes Down-Regulation Dermatology Peripheral blood mononuclear cell Biochemistry Epitope Downregulation and upregulation Antigen Antigens Neoplasm sialyl Lewis x Glycosyltransferase medicine Humans selectin Molecular Biology Cells Cultured Membrane Glycoproteins integumentary system biology food and beverages Glycosyltransferases Cell Differentiation T lymphocyte Cell Biology Th1 Cells Fucosyltransferases Molecular biology Isoenzymes Cytokine skin-homing Cell culture biology.protein HECA-452 |
| Zdroj: | Journal of Investigative Dermatology. 115(2):299-306 |
| ISSN: | 0022-202X |
| DOI: | 10.1046/j.1523-1747.2000.00032.x |
| Popis: | Cutaneous lymphocyte-associated antigen (CLA), which plays a key part in skin homing of human CD4+ memory T cells via CLA/E-selectin binding, is upregulated by IL-12 and downregulated by IL-4. Although alpha1,3-fucosyltransferase VII is essential for synthesis of the CLA carbohydrate epitope, little is known about how the CLA expression is regulated by a number of glycosyltransferases. A 6 wk long-term culture for the in vitro differentiation of naïve Th cells to memory Th1 cells was employed. By repeated activation in the presence of IL-12, naïve T cells differentiated into memory Th1 cells, resulting in the upregulation of CLA expression. The switching of cytokine from IL-12 to IL-4 at three cycles resulted in a marked downregulation of CLA. The transcript levels of 16 glycosyltransferases and P-selectin glycoprotein ligand-1, all considered to be potentially involved in CLA synthesis, were determined after each cycle. The level of CLA expression was well correlated with the amounts of alpha1,3-fucosyltransferase VII and beta1,4-galactosyltransferase I. Both were upregulated by IL-12 and downregulated by IL-4. In particular, alpha1,3-fucosyltransferase VII levels decreased markedly in the presence of IL-4. P-selectin glycoprotein ligand-1 and Core 2 beta1, 6-N-acetylglucosaminyltransferase were progressively up-regulated by repeated IL-12 stimulation, but they were not downregulated by IL-4. The transcript levels of some genes examined were constitutive without any correlation to CLA expression. These results suggest that the level of CLA expression is determined by alpha1, 3-fucosyltransferase VII and beta1,4-galactosyltransferase I, the other enzymes merely participating in the synthesis of CLA. In peripheral blood mononuclear cells, IL-12 and IL-4 profoundly upregulated and downregulated the alpha1,3-fucosyltransferase VII transcripts, respectively, but not the beta1,4-galactosyltransferase I ones, within only 2 h of in vitro culture. This suggested that alpha1,3-fucosyltransferase VII is transcriptionally regulated directly by IL-12 and IL-4. |
| Databáze: | OpenAIRE |
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