γδ intraepithelial lymphocytes acquire the ability to produce IFN-γ in a different time course than αβ intraepithelial lymphocytes.

IF 4.8 4区 医学 Q2 IMMUNOLOGY International immunology Pub Date : 2024-06-05 DOI:10.1093/intimm/dxae034
Shizue Tani-Ichi, Koichi Ikuta
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Abstract

An age-dependent increase in IFN-γ expression by intestinal intraepithelial lymphocytes (IELs) contributes to the acquisition of resistance to infection by pathogens. However, how IELs acquire the ability to produce IFN-γ remains to be elucidated. Here, we report that IELs in the small intestine acquire the ability to rapidly produce IFN-γ at two distinct life stages. TCRαβ+ IELs (αβIELs) started producing IFN-γ at 4 weeks of age, within 1 week after weaning. In contrast, TCRγδ+ IELs (γδIELs) started producing IFN-γ at 7 weeks of age. In mice lacking Eγ4, an enhancer of the TCRγ locus (Eγ4-/- mice), Thy-1+ Vγ5+ γδIELs, a major subpopulation of γδIELs, were specifically reduced and their ability to produce IFN-γ was severely impaired, whereas Vγ2+ γδIELs normally produced IFN-γ. In Eγ4-/- mice, TCR expression levels were reduced in Vγ5+ γδIEL precursors in the thymus but unchanged in the Vγ5+ IELs. Nevertheless, TCR responsiveness in Vγ5+ γδIELs was impaired in Eγ4-/- mice, suggesting that the TCR signal received in the thymus may determine TCR responsiveness and the ability to produce IFN-γ in the gut. These results suggest that αβIELs and γδIELs start producing IFN-γ at different life stages and that the ability of Vγ5+ γδIELs to produce IFN-γ in the gut may be predetermined by TCR signaling in IEL precursors in the thymus.

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γδ上皮内淋巴细胞获得产生 IFN-γ 的能力的时间过程与 αβ 上皮内淋巴细胞不同。
肠上皮内淋巴细胞(IELs)表达的 IFN-γ 随年龄增长而增加,这有助于获得抵抗病原体感染的能力。然而,IELs如何获得产生IFN-γ的能力仍有待阐明。在这里,我们报告了小肠中的 IELs 在两个不同的生命阶段获得快速产生 IFN-γ 的能力。TCRαβ+ IELs(αβIELs)在4周龄时,即断奶后1周内开始产生IFN-γ。相反,TCRγδ+ IELs(γδIELs)在 7 周龄时开始产生 IFN-γ。在缺乏 TCRγ 基因座增强子 Eγ4 的小鼠(Eγ4-/- 小鼠)中,Thy-1+ Vγ5+ γδIELs (γδIELs 的一个主要亚群)特异性减少,其产生 IFN-γ 的能力严重受损,而 Vγ2+ γδIELs 则正常产生 IFN-γ。在 Eγ4-/- 小鼠中,胸腺中 Vγ5+ γδIEL 前体的 TCR 表达水平降低,但 Vγ5+ IELs 的表达水平不变。然而,在 Eγ4-/- 小鼠中,Vγ5+ γδIEL 的 TCR 反应性受损,这表明胸腺中接收的 TCR 信号可能决定了 TCR 反应性和在肠道中产生 IFN-γ 的能力。这些结果表明,αβIELs 和 γδIELs 在不同的生命阶段开始产生 IFN-γ,Vγ5+ γδIELs 在肠道中产生 IFN-γ 的能力可能是由胸腺中 IEL 前体的 TCR 信号决定的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
International immunology
International immunology 医学-免疫学
CiteScore
9.30
自引率
2.30%
发文量
51
审稿时长
6-12 weeks
期刊介绍: International Immunology is an online only (from Jan 2018) journal that publishes basic research and clinical studies from all areas of immunology and includes research conducted in laboratories throughout the world.
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