2001 Fiscal Year Annual Research Report

免疫系ケモカインの生理作用と病的役割の解明

Research Project

Project/Area Number	11470091
Research Institution	Kinki University
Principal Investigator	義江修近畿大学, 医学部, 教授 (10166910)
Co-Investigator(Kenkyū-buntansha)	野見山尚之熊本大学, 医学部, 講師 (00156225) 宮澤正顕近畿大学, 医学部, 教授 (60167757)
Keywords	ケモカイン / ケモカインレセプター / 炎症 / 免疫 / 喘息 / アトピー性皮膚炎 / ノックアウトマウス
Research Abstract	本研究では我々が発見したリンパ球や樹状細胞を標的とする「免疫系ケモカイン」を中心にケモカインスーパーファミリーの生理的および病的機能を明らかにすることを目的とした。今年度のおもな成果は以下の通りである。1、CCR6を介して未熟な樹状細胞やα_4β_7陽性メモリーT細胞を選択的に遊走するケモカインLARC/CCL20は正常皮膚角化細胞からIL-1やTNF-αなどのサイトカイン刺激で誘導され、またアトピー性皮膚炎では皮膚表皮細胞でのLARC産生とCCR6陽性細胞の真皮への浸潤、および血漿LARC値の上昇が見られた。2、LARCの腸管上皮細胞での発現はTNF-αやIL-1などの炎症性サイトカインで誘導され、それは-96〜-87bpに存在するNF-κBサイトとNF-κB分子が関与することを明らかにした。3、CCR4を介してTh2細胞やCLA陽性皮膚指向性エフェクターT細胞を遊走するTARCとMDCはアトピー患者の血漿中で病状と相関して有意に上昇していた。また血小板にはTARCが存在し、その値はアトピー患者では著明に上昇していた。さらにTARCとMDCはともに皮膚角化細胞からIFN-γにより発現誘導された。4、慢性炎症の皮膚組織やリンパ節ではMDC/CCL22を産生する樹状細胞とCCR4を発現するT細胞のクラスターが高頻度に存在することを明らかにし、MDCの免疫応答での重要な役割を示唆した。5、マウスの喘息モデルでTh2型ケモカインTARC/CCL17に対する中和抗体はT細胞や好酸球の肺浸潤を抑制し、また気道過敏性の亢進を阻止した。6、多発性硬化症の髄液中のリンパ球は末梢血中のリンパ球と比較すると、増悪時にはCXCR3やCCR5を発現するTh1が増加しており、緩解期にはCCR5発現細胞の頻度が低下した。7、マウスのMDC、LARC、SLC、などに対する単クローン抗体の作製を行ったが、中和活性を示すものは得られなかった。8、TARCおよびαEインテグリンのノックアウトマウスはBALB/cおよびC57BL/6への戻し交配により純系化した。

Research Products

(14 results)

All Other

All Publications (14 results)

[Publications] Yoshie, O., et al.: "Chemokines in immunity"Advances in Immunology. 78. 57-110 (2001)
[Publications] Nakayama, T., et al.: "Inducible expression of a CC chemokine liver and activation-regulated chemokine (LARC)/macrophage inflammatory protein (MIP)-3α/CCL20 by epidermal keratinocytes and its role in atopic dermatitis"International Immunology. 13・1. 95-103 (2001)
[Publications] Hirai.H, et al.: "Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2"Journal of Experimental Medicine. 193・2. 255-261 (2001)
[Publications] Kawasaki, S., et al.: "Intervention of thymus and activation -regulated chemokine attenuates the development of allergic airway inflammation and hyperresponsiveness in mice"Journal of Immunology. 166・3. 2055-2062 (2001)
[Publications] Hirose, J., et al.: "Versican interacts with chemokines and modulates cellular responses"Journal of Biological Chemistry. 276・7. 5528-5534 (2001)
[Publications] Nomiyama, H., et al.: "Organization of the chemokine genes in the human and mouse major clusters of CC and CXC chemokines : diversification between the two species"Genes and Immunity. 2・2. 110-113 (2001)
[Publications] Misu, T., et al.: "Chemokine receptor expression on T cells in blood and cerebrospinal fluid at relapse and remission of multiple sclerosis : imbalance of Th1/Th2-associated chemokine signaling"J. Neuroimmunology. 114・1-2. 95-103 (2001)
[Publications] Katou, F, et al.: "Macrophage-derived chemokine (MDC/CCL22) and CCR4 are involved in the formation of T lymphocyte-dendritic cell clusters in human inflamed skin and secondary lymphoid tissue"American Journal of Pathology. 158・4. 1263-1270 (2001)
[Publications] Patel, D.D., et al.: "Chemokines have diverse abilities to form solid phase gradients"Journal of Clinical Immunology. 99・1. 43-52 (2001)
[Publications] Iikura, M., et al.: "Chemokine receptors in human basophils : inducible expression of functional CXCR4"Journal of Leukocyte Biology. 70・1. 113-120 (2001)
[Publications] Nomiyama, H., et al.: "Human CC chemokine liver-expressed chemokine/CCL16 is a functional ligand for CCR1,CCR2 and CCR5,and constitutively expressed by hepatocytes"International Immunology. 13・8. 1021-1029 (2001)
[Publications] Miyamasu, M. et al.: "Variations in the human CC chemokine eotaxin gene"Genes and Immunity. 2・8. 461-463 (2001)
[Publications] Terada, N., et al.: "The kinetics of allergen-induced eotaxin level in nasal lavage fluid : its key role in eosinophil recruitment in nasal mucosa"American Journal of Respiratory and Critical Care Medicine. 164・4. 575-579 (2001)
[Publications] Fujiie, S.et al.: "Proinflammatory cytokines induce liver and activation-regulated chemokine/macrophage inflammatory protein-3α/CCL20 in mucosal epithelial cells through NF-κB"International Immunology. 13・10. 1255-1263 (2001)

2001 Fiscal Year Annual Research Report

免疫系ケモカインの生理作用と病的役割の解明

Principal Investigator

義江 修 近畿大学, 医学部, 教授 (10166910)

Research Products

[Publications] Yoshie, O., et al.: "Chemokines in immunity"Advances in Immunology. 78. 57-110 (2001)

[Publications] Nakayama, T., et al.: "Inducible expression of a CC chemokine liver and activation-regulated chemokine (LARC)/macrophage inflammatory protein (MIP)-3α/CCL20 by epidermal keratinocytes and its role in atopic dermatitis"International Immunology. 13・1. 95-103 (2001)

[Publications] Hirai.H, et al.: "Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2"Journal of Experimental Medicine. 193・2. 255-261 (2001)

[Publications] Kawasaki, S., et al.: "Intervention of thymus and activation -regulated chemokine attenuates the development of allergic airway inflammation and hyperresponsiveness in mice"Journal of Immunology. 166・3. 2055-2062 (2001)

[Publications] Hirose, J., et al.: "Versican interacts with chemokines and modulates cellular responses"Journal of Biological Chemistry. 276・7. 5528-5534 (2001)

[Publications] Nomiyama, H., et al.: "Organization of the chemokine genes in the human and mouse major clusters of CC and CXC chemokines : diversification between the two species"Genes and Immunity. 2・2. 110-113 (2001)

[Publications] Misu, T., et al.: "Chemokine receptor expression on T cells in blood and cerebrospinal fluid at relapse and remission of multiple sclerosis : imbalance of Th1/Th2-associated chemokine signaling"J. Neuroimmunology. 114・1-2. 95-103 (2001)

[Publications] Katou, F, et al.: "Macrophage-derived chemokine (MDC/CCL22) and CCR4 are involved in the formation of T lymphocyte-dendritic cell clusters in human inflamed skin and secondary lymphoid tissue"American Journal of Pathology. 158・4. 1263-1270 (2001)

[Publications] Patel, D.D., et al.: "Chemokines have diverse abilities to form solid phase gradients"Journal of Clinical Immunology. 99・1. 43-52 (2001)

[Publications] Iikura, M., et al.: "Chemokine receptors in human basophils : inducible expression of functional CXCR4"Journal of Leukocyte Biology. 70・1. 113-120 (2001)

[Publications] Nomiyama, H., et al.: "Human CC chemokine liver-expressed chemokine/CCL16 is a functional ligand for CCR1,CCR2 and CCR5,and constitutively expressed by hepatocytes"International Immunology. 13・8. 1021-1029 (2001)

[Publications] Miyamasu, M. et al.: "Variations in the human CC chemokine eotaxin gene"Genes and Immunity. 2・8. 461-463 (2001)

[Publications] Terada, N., et al.: "The kinetics of allergen-induced eotaxin level in nasal lavage fluid : its key role in eosinophil recruitment in nasal mucosa"American Journal of Respiratory and Critical Care Medicine. 164・4. 575-579 (2001)

[Publications] Fujiie, S.et al.: "Proinflammatory cytokines induce liver and activation-regulated chemokine/macrophage inflammatory protein-3α/CCL20 in mucosal epithelial cells through NF-κB"International Immunology. 13・10. 1255-1263 (2001)

義江修近畿大学, 医学部, 教授 (10166910)