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Regulatory Effect of IL-4 on Early Th17 Differentiation from Naive T Cells into Stem Cell Memory Th17 Precursors via Modulation of CD31 and CCR6 Expression
https://showa.repo.nii.ac.jp/records/3461
https://showa.repo.nii.ac.jp/records/3461a05468b7-5c38-4156-a24a-3bc9bf4dfddc
名前 / ファイル | ライセンス | アクション |
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S32_135.pdf (840.1 kB)
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Item type | 学内発行雑誌 / Departmental Bulletin Paper(1) | |||||
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公開日 | 2020-08-19 | |||||
タイトル | ||||||
タイトル | Regulatory Effect of IL-4 on Early Th17 Differentiation from Naive T Cells into Stem Cell Memory Th17 Precursors via Modulation of CD31 and CCR6 Expression | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ | departmental bulletin paper | |||||
著者 |
MAEDA, Kohei
× MAEDA, Kohei× TANIOKA, Toshihiro× IWAMOTO, Sanju |
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書誌情報 |
The Showa University journal of medical sciences 巻 32, 号 2, p. 135-145, 発行日 2020-07 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Although antigen-specific T helper (Th) cells are developed from naive T cells, human Th17 cells are not derived from naive CD4+ T cells unlike murine cells. Therefore, the source of human Th17 cells has remained unresolved. In this study, we assessed the early differentiation pathway of human Th17 cells from CD31+ thymic naive T cells into stem cell memory CCR6+ Th17 precursors and the regulation of this process by cytokines. Peripheral blood mononuclear cells were isolated from healthy volunteers. We found that only CD31- CCR6+ naive type CD4+ T cells had the ability to produce IL-17A in response to Th17-inducing stimuli. A cell tracking assay using CD31+ CCR6- cells labeled with carboxyfluorescein diacetate succinimidyl ester revealed that CD31- CCR6+ Th17 precursors were derived from CD31+ CCR6- thymic naive T cells. CD31 is known to suppress IL-17 production by interfering with downstream T cell receptor (TCR) signaling molecules including Lck, which is essential for IL-17 production. The inactive form of Lck was much higher in CD31+ T cells than CD31- T cells after TCR stimulation. In experiments of cytokine-mediated modulation of Th17 cell differentiation, IL-4 suppressed the conversion of CD31+ CCR6- naive T cells into CD31- CCR6+ Th17 precursors by upregulating CD31 expression and suppressing CCR6 expression. In conclusion, CD31- CCR6+ Th17 precursors could be sourced from CD31+ CCR6- naive T cells, and IL-4 regulated the early Th17 differentiation. Our findings provide novel insights into the regulation of differentiation of naive CD4+ T cells into Th17 cells in humans. Furthermore, our results may provide hints for further elucidation of the differentiation process of Th17 cells and of the pathology of Th17 cell-related diseases. | |||||
DOI | ||||||
関連識別子 | 10.15369/sujms.32.135 | |||||
出版者 | ||||||
出版者 | Showa University Society | |||||
ISSN | ||||||
収録物識別子 | 2185-0968 | |||||
著者版フラグ | ||||||
出版タイプ | VoR |