초록 ▼

1. 혈관·면역세포 교신 연구 및 다양한 혈관질환 모델 구축을 위한 다중유전자변형마우스 제작 및 표현형 분석
(1) 동맥경화 발병과정에서 plasmacytoid 수지상 세포를 특이적으로 결핍시키는 조건적 다중유전자변형 마우스 제작 및 혈관·면역세포 기능 관련 표현형 분석
(2) ApoE 유전자적중마우스와 새로운 신호전달 인자 후보 CD137, Oasl1, Prx1, Prx3, Prx5 유전자적중마우스와의 교배를 통한 동맥경화모델 구축 및 혈관·면역세포 기능 관련 표현형 분석
2. 혈관질환 방어를 위한 면역세포 특이적

1. 혈관·면역세포 교신 연구 및 다양한 혈관질환 모델 구축을 위한 다중유전자변형마우스 제작 및 표현형 분석
(1) 동맥경화 발병과정에서 plasmacytoid 수지상 세포를 특이적으로 결핍시키는 조건적 다중유전자변형 마우스 제작 및 혈관·면역세포 기능 관련 표현형 분석
(2) ApoE 유전자적중마우스와 새로운 신호전달 인자 후보 CD137, Oasl1, Prx1, Prx3, Prx5 유전자적중마우스와의 교배를 통한 동맥경화모델 구축 및 혈관·면역세포 기능 관련 표현형 분석
2. 혈관질환 방어를 위한 면역세포 특이적인 신호전달 인자 규명
(1) 조절 T 림프구의 유도를 통한 plasmacytoid 수지상 세포의 동맥경화 방어기전 규명
(2) 초기 동맥경화 및 급성대장염 발병과정에서 면역세포 특이적인 CD137 기능 연구
3. 동맥경화 발병과정에서 혈관·면역세포 교신(cross talk)용 신호전달 인자로서 Retnla, Oasl1, Ninj1 기능 규명
4. 동맥경화 발병과정에서 혈관질환을 촉진하는 인자들을 제거하는 항산화 효소의 대식세포 특이적인 자가포식 흐름을 통한 혈관세포 상해(injury) 방어 기전 규명

(출처 : 보고서 요약서 3p)

Abstract ▼

□ Purpose
Purposes : “To elucidate the new network between the vascular and immune cells in the regulation of vascular diseases, and to find the inhibitory mechanisms for vascular cell injury”
Specific aims : (1) To find the specific immune cells which inhibit the progression of vascular disea

□ Purpose
Purposes : “To elucidate the new network between the vascular and immune cells in the regulation of vascular diseases, and to find the inhibitory mechanisms for vascular cell injury”
Specific aims : (1) To find the specific immune cells which inhibit the progression of vascular diseases using the genetically modified mice. (2) To elucidate the regulatory factors for signaling of cross talk between the vascular and immune cells, and the defense mechanisms to vascular cell injury. (3) To suggest the new molecular mechanisms for the therapy of vascular diseases.

□ contents
The recent studies of the vascular and immune cells have focused on the inflammatory molecule accelerating the progress of athersclerotic lesions. This study team firstly reported the existence of immune cells (dendritic cells) which restrain vascular diseases on a basis of hypothesis that specific immune cells are able to suppress the progress of atherosclerotic lesions (Immunity, Nov.2011). On the ground of these previous findings, we study cross talk between vascular and immune cells normalizing blood vessel function; and do research for new groundwork to identify molecular regulation in a cell to overcome the injury of vascular cells.
Specific aim (1)
① To analyze characteristics of cells deposited on the normal and abnormal blood vessel, and interactions with blood vessel cells
② To produce tissues (immune cells)-specific transgenic animals for investigation of immune cells and signaling modiilators normalizing vascular cell functions
③ To analyze and profile immune cell types normalizing functions of vascular cells
Specific aim (2)
① To identify the adhesion molecule and the secretory signal transduction modulators, between the vascular and immune cells
② To clarify the defense mechanisms through removal of disease-promoting factor (cell or signaling factor) within the vascular tissue
③ To elucidate the defense mechanisms to cell injury via regulation of autophagy between the vascular and immune cell
Specific aim (3)
① To propose the treatment with factors and substances to normalize the function of vascular cells
② To establish the treatment using immune cells to normalize the function, of vascular, cells
③ To establishment of vascular disease suppression methods using antibodies and peptides

□ Developement results
(1) Generation and phenotyping of genetically modified mouse model for vascular diseases
① Generation and phenotyping of depletion of pDC or Treg in Ldlr knock-out mice
② Generation and phenotyping of multiple knock-out mice in acute colitis model
③ Generation and phenotyping of multiple knock-out mice in stroke model
(2) Identification of the adhesion molecule and the secretory signal transduction modulators, between the vascular and immune cells
① Aortic plasmacytoid dendritic cells protect against atherosclerosis by induction of regulatory T cells
② Functional study of CD137 in the early stage of atherosclerosis
③ Functional study of CD137 in acute colitis
(3) Clarification of the defense mechanisms through removal of disease-promoting factor (cell or signaling factor) within the vascular tissue
① The mechanism of vascular immune cell regulation by Retnla gene function in the arteriosclerosis
② The mechanism of signal transduction for vascular immune cell communication by Ninj1 in the pathogenesis of atherosclerosis
③ Functional analysis of Oasll in vascular immune cells during the onset of atherosclerosis
(4) Elucidation of the defense mechanisms to cell injury via regulation of autophagy between the vascular and immune cell
① Prx1 deficiency reduces cholesterol efflux via impaired macrophage lipophagic flux
② The function of Prx1 in the brain immune cells during the onset of stroke
③ Functional analysis of Oasll in vascular immune cells during the onset of atherosclerosis

□ Expected Contribution
(1) To produce core technology for development of new vascular treatments and drugs by finding molecular mechanism and type of immune cells normalizing function of vascular cells.
(2) To make infrastructure of translational research applicable to human body with development of transgenic animals deficient in specific protein or immune cells.

(출처 : SUMMARY 5p)

목차 Contents

• 표지 ... 1
• 제출문 ... 2
• 보고서 요약서 ... 3
• 국 문 요 약 문 ... 4
• SUMMARY ... 5
• 목차 ... 6
• 1. 연구개발 목표 및 내용(연구계획서상에 작성된 목표 및 내용을 기술) ... 7
• 가. 최종목표 ... 7
• 나. 단계목표(당초목표 및 수정·보완 목표) ... 7
• 다. 당초 목표의 수정·보완(중요 연구변경) 사유 ... 7
• 라. 2단계 연차별 연구목표 및 내용 ... 8
• 2. 연구 추진전략 및 방법 ... 9
• 3. 주요 연구개발결과 ... 12
• 가. 계획대비 달성도 ... 12
• 나. 대표적 연구업적 ... 51
• 다. 현 단계 달성된 연구결과의 세계적 연구 위상 ... 52
• 라. 기타 계획하지 않은 연구성과 ... 56
• 마. 연구역량 향상 정도 ... 60
• 바. 세계적 연구리더로서 연구책임자의 성장 정도 ... 62
• 4. 연구수행에 따른 문제점 및 개선방향 ... 62
• 5. 연구개발성과 현황 ... 63
• 6. 국가과학기술종합정보시스템에 등록한 연구시설·장비 현황 ... 77
• 7. 기타사항 ... 77
• 끝페이지 ... 78