2005 Fiscal Year Final Research Report Summary
T cell homing control by fucosyltransferases VII/IV
| Project/Area Number |
16591118
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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 |
HAYAKAWA Kazuhito Kyorin University School of Medicine, Associate Professor, 医学部, 助教授 (50146669)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUKAWA Yoshiko Kyorin University, School of Medicine, Assistant, 医学部, 助手 (50301479)
TAKAHASHI Ryo Kyorin University, School of Medicine, Assistant, 医学部, 助手 (00317091)
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| Project Period (FY) |
2004 – 2005
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| Keywords | fucosyltransferase / FucT-IV / FucT-VII / E-selectin ligand / CLA / IL-4 / IL-12 / homing |
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| Research Abstract |
1.Using human lymphocyte cell lines transfected with FucT-VII or FucT-IV cDNA, we examined E-selectin ligand(ESL) and CLA expression with enzyme-immunohistochemical techniques. As a result, induction of ESL alone occurred in FucT-IV transfectant, while both ESL and CLA expression were observed in FucT-VII transfectant.
We next examined sequential expressions of ESL, CLA and fucosyltransferases during in vitro differentiation from naive to memory CD4^+T cells..
2.ESL^+CLA^- cells appeared at early stages of differentiation. As differentiation progressed, ESL^<++> CLA^+ cells increased.
3.At early stages of differentiation, CD4^+T cells expressed both FucT-IV and FucT-VII. As differentiation progressed, FucT-IV was down-regulated, leading to increase in CD4^+T cells with FucT-VII dependent phenotype(ESL^<++>CLA^+)
4.When ESL^+CLA^-CD4^+T cells were transferred to IL-12-rich milieu, the shift to the phenotype ESL^<++>CLA^+ was observed. However, when ESL^+CLA^- cells were moved to IL-4-rich milieu, similar shift did not occur, and FucT-VII expression was remarkably down-regulated. It appeared likely that down-regulation of FucT-VII expression may inhibit further T cell differentiation. FucT-VII was up-regulated on these cells, leading to induction of ESL^<++>CLA^+ phenotype when they were moved to IL-12-rich milieu. It is known that in atopic dermatitis, peripheral blood shows IL-4-rich milieu, on the other hand, the lesional skin does IL-12-rich one. These environments may induce continuous migration of CD4^+T lymphocytes to the lesional skin.
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