| Item type |
学内発行雑誌 / Departmental Bulletin Paper(1) |
| 公開日 |
2020-08-19 |
| タイトル |
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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 |
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言語 |
en |
| 言語 |
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|
言語 |
eng |
| 資源タイプ |
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資源タイプ |
departmental bulletin paper |
| 著者 |
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 |
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内容記述タイプ |
Abstract |
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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 |
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関連タイプ |
isIdenticalTo |
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関連識別子 |
10.15369/sujms.32.135 |
| 出版者 |
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出版者 |
Showa University Society |
| ISSN |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
2185-0968 |
| 出版タイプ |
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出版タイプ |
VoR |
S32_135.pdf (840.1 kB)
