DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Kim, Seyun | - |
dc.contributor.advisor | 김세윤 | - |
dc.contributor.advisor | Kim, Hail | - |
dc.contributor.advisor | 김하일 | - |
dc.contributor.author | 육채민 | - |
dc.date.accessioned | 2022-04-21T19:33:38Z | - |
dc.date.available | 2022-04-21T19:33:38Z | - |
dc.date.issued | 2020 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=986301&flag=dissertation | en_US |
dc.identifier.uri | http://hdl.handle.net/10203/295598 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 의과학학제전공, 2020.2,[vii, 112 p. :] | - |
dc.description.abstract | Inositol polyphosphate multikinase (IPMK) physiologically creates IP4 and IP5. IPMK is also known as an important phosphatidylinositol 3 kinase (PI3K) that forms PIP3 which activates Akt and influences cell growth. Whereas actions of classical PI3K enzymes are well-identified in lymphocytes, there are no reports to study whether IPMK is involved in diverse steps of CD4+ T cell biology. I first identified that the expression level of IPMK is highly induced in a distinct Th17 subset. Also, production of IL-17A under Th17 differentiation condition are highly attenuated in IPMK-/-CD4+ T cells relative to control cells. In in vivo EAE model, IPMK deficiency in T cells showed attenuated clinical outcome, indicating reduced Th17 immune response. Transcriptional profiles have revealed IPMK-/-CD4+ T cells show marked increase of Foxp3 gene under Th17 differentiation condition. I identified IPMK regulates phosphorylation of STAT3 activated IL-6 receptor signaling via socs3 inhibition. Thus, the finding of this study is the specific molecular mechanism of IPMK signaling actions in CD4+ T cells in distinct types of Th17 cells.Inositol pyrophosphates 5-IP7, formed by inositol hexakisphosphate kinases (IP6Ks), are highly energetic inositol metabolites. 5-IP7 is a physiological inhibitor of AKT, preventing translocation of AKT to the membrane. Whereas action of IP6K1 are well-known in innate immune cells, neutrophils, there are no research about adaptive immune system like CD4+ T cells. Here, I assessed that IP6K1 protein was highly expressed in CD4+ T cells 48 hours after TCR stimulation. Surprisingly, IP6K1-/-CD4+ T cells showed increase of apoptotic cell death at a late phase of TCR stimulation. Furthermore, IP6K1-/-CD4+ T cells displayed attenuated phosphorylation of AKT unlike previous reporting. Transcription factor inducing apoptosis, c-Jun, was enhanced in IP6K1-deficient CD4+ T cells at a late stage of TCR stimulation. IP6K1 has, therefore, a role for cellular survival signaling in CD4+ helper T cells. | - |
dc.language | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | IPMK▼aCD4+ T cells▼aTh17 cells▼aDifferentiation▼aSTAT3 signaling▼aEAE▼aIP6K1▼aApoptosis▼aSurvival | - |
dc.subject | 이노시톨 다인산 멀티키나아제▼a17형 도움 T 세포▼a분화▼a자가면역질환▼a이노시톨 헥사키스포스페이트▼a세포사멸▼a생존신호전달 | - |
dc.title | Identification of roles of inositol polyphosphate metabolism in the regulation of functions and differentiation of CD4 helper T cells | - |
dc.title.alternative | 이노시톨 다인산 대사의 CD4 도움 T 세포 기능 및 분화 조절 역할 규명에 대한 연구 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 325007 | - |
dc.description.department | 한국과학기술원 :의과학학제전공, | - |
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