13 research outputs found
Wnt μ νΈμ μν μΈκ° Th17 μΈν¬ λΆν μ‘°μ λ° NKT μΈν¬ 리κ°λμ λΉκ° λ°±μ adjuvant νμ© μ°κ΅¬
Wnt/Ξ²-catenin μ νΈλ μ΄κΈ° λ°°λ°μ, μ’
μ νμ± λ±μ κ³Όμ λμ μ€μν μν μ νλ©°, T μΈν¬μμλ Th2 μΈν¬λ‘μ λΆνλ₯Ό μ΄μ§νλ€. κ·Έλ¬λ μΈκ° Th17 μΈν¬μ λΆνμ μ μ§μ μμ΄ Wnt μ νΈμ μν μ μμ§κΉμ§ λͺ
ννμ§ μλ€. λ³Έ μ°κ΅¬μμλ ν΄νμ± κ΄μ μΌ νμμ λΉκ΅νμ¬ λ₯λ§ν°μ€ κ΄μ μΌ νμμ κ΄μ νμ‘μμ IL-17μ΄ μ¦κ°λμ΄ μμΌλ©°, μ΄λ Wnt/Ξ²-catenin κ²½λ‘μ μ΅μ μ μΈ sFRP1λλμ μ¦κ°μ μκ΄κ΄κ³κ° μμμ κ΄μ°°νμλ€. T μΈν¬ μμ©μ²΄λ₯Ό 맀κ°λ‘ ν μκ·Ήμμ sFRP1μ 첨κ°λ naΓ―ve CD4+μ memory T μΈν¬μ μν IL-17 μμ°μ νμ ν μ¦κ°μμΌ°λ€. λμ±μ΄ Th17 λΆν 쑰건μμλ, sFRP1 첨κ°κ° TGF-Ξ²μ λν μꡬλ₯Ό νμ ν κ°μμμΌ°λ€. λ©μ»€λμ¦μ μΌλ‘, sFRP1μ TGF-Ξ² μκ·Ήμ CD4+ T μΈν¬μμ Smad2/3μ μΈμ°νλ₯Ό μ¦κ°μμΌ°μΌλ©°, TGF-Ξ² μ νΈμ μ΅μ λ sFRP1μ Th17 μ΄μ§ νμ±μ μ¬λΌμ§κ² νμλ€. μ’
ν©μ μΌλ‘ μ΄λ² μ°κ΅¬ κ²°κ³Όλ μΈκ° Th17 μΈν¬ λΆνμ κ°λ ₯ν μ λμ λ‘μ sFRP1μ κ³ μ ν κΈ°λ₯μ 보μ¬μ£Όμλ€. λ°λΌμ sFRP1μ μΈκ°μμ Th17μΈν¬λ₯Ό 맀κ°λ‘ νλ μ§νμ μΉλ£μ μ λ§ν νμ μ΄ λ μλ μμ κ²μΌλ‘ κΈ°λλλ€.
Ξ±-galactosylceramide (Ξ±-GalCer)λ μμ νκ³ ν¨κ³Όμ μΈ λΉκ° λ°±μ adjuvantλ‘ μκ³Ό λ°μ΄λ¬μ€ κ°μΌμ λν ν¨κ³Όμ μΈ λ°©μ΄λ©΄μλ°μμ μ λνλ€. λ³Έ μ°κ΅¬μμλ CD1d/λΉμ§μ§ ꡬ쑰μ κ·Όκ±°νμ¬ κ°μ§κ΅¬μ‘°λ₯Ό ν¬ν¨νλλ‘ μ€κ³λ λ κ°μ§ Ξ±-GalCer μ λ체λ€, KBC-007κ³Ό KBC-009μ λΉκ° λ
κ° λ°±μ adjuvantλ‘μμ ν¨κ³Όλ₯Ό νκ°νμλ€. μ΄λ€ μ λ체λ€μ Ξ±-GalCerλ³΄λ€ μ©ν΄λκ° κ°μ λμμΌλ©° λ§μ°μ€μ μΈκ°μ μμ°μ΄ν΄ T μΈν¬λ₯Ό κ°νκ² μκ·Ήνμλ€. in vivo νμ² μ¬μ΄ν μΉ΄μΈ λΆμ κ²°κ³Ό μλ‘ λ€λ₯Έ μ¬μ΄ν μΉ΄μΈ λΆλΉ νλ‘νμ μ λνμ¬, KBC-009λ Th1/Th2 μ¬μ΄ν μΉ΄μΈμ λͺ¨λ μ λν λ°λ©΄ KBC-007μ Th2λ‘ νΈν₯λ μ¬μ΄ν μΉ΄μΈ λ°μμ μ λνμλ€. λΆνμ±νλ λ
κ° λ°μ΄λ¬μ€ A/PR/8/34 (PR8)μ ν¨κ» Ξ±-GalCer μ λ체λ₯Ό λ¨μΌ ν¬μ¬λ‘ λ©΄μννμμ λ μ μ κ³Ό μ λ§λΆμμμ νμ νΉμ΄μ μΈ μ²΄μ‘μ±κ³Ό μΈν¬μ± λ©΄μ λ°μμ΄ κ°νλμλ€. νΉν, KBC-009λ λΆνμ±νλ PR8 λ¨λ
λ©΄μνμ λΉκ΅νμ¬ νμ ν μ¦κ°λ μ μ IgGμ μ λ§ IgA ν체 μκ°μ μΈν¬ λ
μ± T μΈν¬ μμ±μ μ λνλ λ± κ°ν adjuvant νμ±μ λνλ΄μλ€. μ΄μ λμ‘°μ μΌλ‘ KBC-007μ 첨κ°λ PR8 νΉμ΄μ μΈ λ©΄μ λ°μμ λ―Έλ―Ένκ² μ¦κ°μμΌ°λ€. λ°μ΄λ¬μ€ κ°μΌμ λν KBC-009μ λ°©μ΄ ν¨κ³Όλ Ξ±-GalCerμ κ²½μ°μ μ μ¬νμλ€. μ΄λ₯Ό ν΅νμ¬ κ°μ§κ΅¬μ‘°λ₯Ό ν¬ν¨ν Ξ±-GalCer μ λμ²΄κ° λ
κ° λ°μ΄λ¬μ€ κ°μΌμ λν λ°©μ΄ λ©΄μ λ°μμ μ λν μ μλ ν¨κ³Όμ μΈ μ λ§ adjuvantλ‘ μ¬μ©λ μ μλ€λ κ²μ νμΈνμλ€.Wnt/Ξ²-catenin signaling plays a crucial role during embryogenesis and tumorigenesis and in T cells, promotes the differentiation of Th2 cells. However, the role of Wnt signals in the differentiation and maintenance of human Th17 cells remains poorly understood. We found that the higher levels of IL-17 in the synovial fluid of rheumatoid arthritis (RA) patients compared to osteoarthritis (OA) patients were associated with a higher concentration of sFRP1, an inhibitor of the Wnt/Ξ²-catenin pathway. The addition of sFRP1 during TCR-mediated stimulation induced a significant increase in IL-17 production by both naive CD4+ and memory T cells. Moreover, under Th17-differentiation conditions, the addition of sFRP1 significantly reduced the requirement for TGF- Ξ². Mechanistically, we observed that sFRP1 significantly enhanced the phosphorylation of Smad2/3 in CD4+ T cells upon TGF- Ξ² stimulation and that blocking TGF-Ξ² signaling abolished the Th17-promoting activity of sFRP1. Our findings reveal a novel function for sFRP1 as a potent inducer of human Th17 cell differentiation. Consequently, sFRP1 may represent a promising target for the treatment of Th17-mediated disease in humans.
Ξ±-Galactosylceramide (Ξ±-GalCer) is a safe and effective adjuvant for nasal vaccines and induces protective immune responses against tumors and viral infections. In our previous study, the fatty acyl chains of Ξ±-GalCer were modified based on the CD1d/glycolipid structure to generate Ξ±-GalCer analogues with branched acyl chains. In this study, two Ξ±-GalCer analogues, KBC-007 and KBC-009, that have different branched chain lengths were prepared and evaluated for their efficacy as nasal influenza vaccine adjuvants. These analogues displayed improved solubility over Ξ±-GalCer and potently stimulated NKT cells in both murine and in vitro human systems. Examination of serum cytokines in vivo revealed that these analogues elicited different cytokine release profiles compared to Ξ±-GalCer. KBC-009 induced both Th1/Th2 cytokines, whereas KBC-007 induced a more Th2-polarized cytokine response with diminished IFN-Ξ³ production. We found that a single immunization of inactivated influenza virus A/PR/8/34 (PR8) combined with Ξ±-GalCer analogues enhanced PR8-specific humoral and cellular immune responses in both systemic and mucosal compartments. Notably, KBC-009 exhibited potent adjuvant effects, inducing significantly higher systemic IgG and mucosal IgA antibody titers and enhancing cytotoxic T lymphocyte generation when compared to immunization with inactivated PR8 alone. In contrast, addition of KBC-007 to inactivated PR8 only marginally increased PR8-specific immune responses. The protective effect of KBC-009 against challenge infection was comparable to the effect produced by Ξ±-GalCer. These results suggest that an Ξ±-GalCer analogue with a branched acyl chain could be used as an effective mucosal adjuvant for the induction of protective immune responses against influenza virus infection.Docto
νκ΅ μλμ§ μ°μ μ μ λ§κ³Ό λ―Έλμ λ΅
Thesis(master`s)--μμΈλνκ΅ κ²½μμ λ¬Έλνμ :κ²½μνκ³Ό Global MBAμ 곡,2007.8Maste
A study for the application of the replicated crossover designs to the assessment of bioequivalence μλ¬Όνμ λλ±μ± νκ°μ μμ΄μ λ°λ³΅ κ΅μ°¨μνλ²μ νμ©μ κ΄ν μ°κ΅¬
Thesis (master`s)--μμΈλνκ΅ λ³΄κ±΄λνμ :보건νκ³Ό,1999.Maste