DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Jeong, Won-Il | - |
dc.contributor.advisor | 정원일 | - |
dc.contributor.author | Shim, Young-Ri | - |
dc.date.accessioned | 2023-06-23T19:33:25Z | - |
dc.date.available | 2023-06-23T19:33:25Z | - |
dc.date.issued | 2022 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=1006542&flag=dissertation | en_US |
dc.identifier.uri | http://hdl.handle.net/10203/309051 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 의과학대학원, 2022.2,[iv, 59 p. :] | - |
dc.description.abstract | About 80 % of patients with alcoholic steatosis do not progress into alcoholic steatohepatitis, suggesting the existence of unknown protective mechanisms. Recently, some macrophages are known to have anti-inflammatory roles, but their phenotypes and origins are unveiled. I investigated the sub-population of macrophages showing anti-inflammatory roles through scRNA-Seq, the mechanism of monocyte egress from bone marrow (BM), and the regulatory effects of mesenchymal stromal cells (MSCs) on BM monocytes. In alcohol-fed mouse liver, scRNA-Seq revealed high expression of interleukin-1 type II receptor (IL-1R2), decoy receptor of IL-1β in Ly6C$^{low}$ macrophages. Besides, BM leptin receptor (LepR)$^+$ MSCs could metabolize alcohol by alcohol dehydrogenase, and expressed cystine-glutamate anti-porter xCT for glutamate excretion and chemokines (CXCL9 and 10) that recruited CXCR3$^+$ natural killer (NK) cells and stimulated metabotropic glutamate receptor 5 (mGluR5) in NK cells, leading to enhanced production of interferon-γ (IFN-γ). In turn, IFN-γ down-regulated CX3C chemokine receptor 1 (CX3CR1) expression in Ly6C$^{low}$ monocytes bound to chemokine (C-X3-C motif) ligand 1 (CX3CL1)$^+$ MSCs, consequently inducing egress of Ly6C$^{low}$ monocytes into the blood. In conclusion, glutamate LepR$^+$ MSCs granted egress license on IL-1R2$^+$ Ly6C$^{low}$ monocytes through NK/IFN-γ-mediated inhibition of CX3CR1, suggesting a potential therapeutic inter-organ crosstalk between BM and liver in alcohol-related liver disease (ALD). | - |
dc.language | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | Alcohol-related liver disease▼aMonocyte▼aMacrophage▼aIntereukin-1 type II receptor (IL-1R2)▼aBone marrow▼aLepR+ Mesenchymal stromal cell▼aGlutamate▼aNK cell▼aInterferon- γ (IFN-γ)▼aCX3C chemokine receptor 1 (CX3CR1) | - |
dc.subject | 알코올성 간질환▼a단핵구▼a대식세포▼a인터루킨-1 수용체 2형 (IL-1R2)▼a골수▼a렙틴수용체+ 중간엽기질세포▼a글루타메이트▼a자연살해세포▼a인터페론-감마▼aCX3C 케모카인 수용체 1 (CX3CR1) | - |
dc.title | Study of bone marrow-liver axis mediated by IL-1R2+ macrophage in alcohol-related liver disease | - |
dc.title.alternative | 알코올성 간질환 발달시 IL-1R2 양성 대식세포 매개 골수-간 축의 역할 규명 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 325007 | - |
dc.description.department | 한국과학기술원 :의과학대학원, | - |
dc.contributor.alternativeauthor | 심영리 | - |
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