DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Shin, Eui-Cheol | - |
dc.contributor.advisor | 신의철 | - |
dc.contributor.advisor | Park, Su-Hyung | - |
dc.contributor.advisor | 박수형 | - |
dc.contributor.author | Kim, Jong Hoon | - |
dc.contributor.author | 김종훈 | - |
dc.date.accessioned | 2017-03-29T02:47:27Z | - |
dc.date.available | 2017-03-29T02:47:27Z | - |
dc.date.issued | 2016 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=663161&flag=dissertation | en_US |
dc.identifier.uri | http://hdl.handle.net/10203/222272 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 의과학대학원, 2016.8 ,[v, 62 p. :] | - |
dc.description.abstract | Psoriasis is one of the most common chronic inflammatory diseases and clinical findings show scal-ing plaques on the erythematous patches on the skin. Recently, interleukine (IL)-17-producing T cells have been shown to play a critical role in psoriatic inflammation. IL-17-producing T cells is activated under the stimulation of cytokines such as IL-23 or T-cell receptor (TCR) engagement. IL-23 has been targeted for treatment of psoriasis using an antibody against p40 | - |
dc.description.abstract | however, there is no efficient drug for targeting TCR-mediated activation in psoriasis. Programmed cell death-1 (PD-1) is a co-inhibitory recep-tor expressed on T cells and inhibits TCR-mediated signaling when interacts with programmed cell death ligand 1 (PD-L1) or 2 (PD-L2). Also, PD-1 expression on the cell surface is increased when the cell re-ceive the repetitive TCR stimulation. Nevertheless, it remains to be elucidated whether PD-1 is overex-pressed on T cells in psoriasis and whether PD-1 agonist alleviates psoriatic inflammation. During IMQ-induced psoriatic inflammation, PD-1 is overexpressed on $CD27-V\gamma 1- \gamma \delta T$ cells. In the $CD27-V \gamma 1- \gamma \delta T$ cell population, $V \gamma 4- \gamma \delta T$ cells with $V \gamma 6 mRNA$ expression showed a high level of PD-1 expression. Further, these $PD-1^{hi}V \gamma 4^-(V \gamma 6^+) \gamma \delta T$ cells were specialized for TCR-induced IL-17A produc-tion, which was inhibited by PD-L1-Fc protein treatment. In IMQ-treated mice, PD-L1-Fc protein reduced psoriatic inflammation when given alone and enhanced the therapeutic effect of anti-p40 when given in combination. Further, PD-1 expression on $IL-17A^+ T$ cells was confirmed in the skin from psoriasis pa-tients. Human PD-L1-Fc protein inhibits IL-17A production and proliferation of $PD-1^+CD4 T$ cells. In conclusion, PD-1 is overexpressed in IL-17A-producing T cells in both IMQ-treated mice and psoriasis patients. PD-1-expressing $IL-17A^+ T$ cells are inhibited by the treatment of PD-L1-Fc protein in mice and human. Moreover, PD-L1-Fc protein alleviates psoriatic inflammation in IMQ-treated mice. | - |
dc.language | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | psoriasis | - |
dc.subject | programmed cell death-1 | - |
dc.subject | programmed cell death ligand 1 | - |
dc.subject | interleukin 17A | - |
dc.subject | T cell | - |
dc.subject | 건선 | - |
dc.subject | PD-1 | - |
dc.subject | PD-L1 | - |
dc.subject | 인터루킨 17A | - |
dc.subject | T 세포 | - |
dc.title | (The) role of programmed cell death ligand 1 in the regulation of psoriatic inflammation | - |
dc.title.alternative | 건선에서 PD-L1의 염증조절 역할 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 325007 | - |
dc.description.department | 한국과학기술원 :의과학대학원, | - |
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