2020 Fiscal Year Final Research Report
New pharmacological effect of tofacitinib via modulating macrophage function
Project/Area Number |
19K23805
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund |
Review Section |
0801:Pharmaceutical sciences and related fields
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Research Institution | Health Sciences University of Hokkaido |
Principal Investigator |
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Project Period (FY) |
2019-08-30 – 2021-03-31
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Keywords | トファシチニブ / マクロファージ / MHC II / CIITA |
Outline of Final Research Achievements |
Tofacitinib is the first Janus kinase inhibitor approved for the treatment of rheumatoid arthritis. Although macrophages are critically involved in the pathogenesis of rheumatoid arthritis, very few studies have reported the influence of tofacitinib on macrophage activation. In the present study, we examined the effect of tofacitinib on the expression of major histocompatibility complex class II (MHC II) and co-stimulatory molecule CD86 in macrophages. IFN-γ induces the cell surface expression of MHC II and CD86. Tofacitinib treatment significantly upregulated IFN-γ-induced expression of MHC II, while decreased the expression of CD86, hence CD86- MHC II+ cells were induced. We anticipate the contribution of induction of CD86- MHC II+ macrophages by tofacitinib in its antirheumatic action, because antigen presentation by MHC II without co-stimulation leads to T cell ignorance, a process known as peripheral immune tolerance.
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Free Research Field |
生物系薬学
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Academic Significance and Societal Importance of the Research Achievements |
Tofacitinib 存在下 IFN-γ 刺激による CD86陰性MHCI陽性 (CD86-MHCI+) マクロファージの誘導の発見は,tofacitinibの新規抗リウマチ作用の可能性を示した.一方で,CD86-MHCI+ マクロファージによる末梢性免疫寛容誘導も示唆される.従って,tofacitinib による易感染性など有害事象発生のメカニズムの一端となる可能性が示唆された. Tofacitinib をはじめとする JAK 阻害薬の免疫疾患に対する期待は大きい.CD86-MHCI+ マクロファージ機能についてのさらなる研究によって JAK 阻害薬による過剰免疫の制御方法確立に貢献できる.
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