小柯机器人

美国匹兹堡大学医学院Dario A. A. Vignali研究团队取得一项新突破。他们发现IFNγ-诱导的th1样调节性T细胞（T_reg）调控抗病毒反应。相关论文于2023年3月16日发表在《自然—免疫学》杂志上。

研究表明，在感染淋巴细胞性脉络丛脑膜炎和甲型流感病毒时，T_reg细胞暴露于干扰素γ（IFNγ）其获得稳定和功能性效应样状态。限制性缺失IFNγ受体（由Ifngr1编码）但不缺失白细胞介素12（IL12）受体（由Il12rb2编码）的T_reg细胞，会阻止T_H1样极化（T-bet、CXC基序趋化因子受体3和IFNγ表达降低）并促进T_H2样极化（GATA-3、CCR4和IL4的表达增加）。T_H1样T_reg细胞限制了CD8⁺ T细胞的效应功能、增殖和急性或慢性感染期间记忆T细胞的形成。

这些发现为病毒感染期间T_reg细胞如何感知环境（如IFNγ）炎症线索提供了见解，从而为效应免疫反应提供指导。这种调节回路可防止长时间的免疫炎症反应，并重塑记忆T细胞反应的质量和数量。

研究人员表示，T_reg是一种免疫抑制细胞群，需要通过抗炎细胞因子、抑制剂受体和破坏代谢来维持外周耐受并防止免疫细胞对组织造成损伤。

附：英文原文

Title: IFNγ-induction of TH1-like regulatory T cells controls antiviral responses

Author: Gocher-Demske, Angela M., Cui, Jian, Szymczak-Workman, Andrea L., Vignali, Kate M., Latini, Julianna N., Pieklo, Gwen P., Kimball, Jesse C., Avery, Lyndsay, Cipolla, Ellyse M., Huckestein, Brydie R., Hedden, Lee, Meisel, Marlies, Alcorn, John F., Kane, Lawrence P., Workman, Creg J., Vignali, Dario A. A.

Issue&Volume: 2023-03-16

Abstract: Regulatory T (Treg) cells are an immunosuppressive population that are required to maintain peripheral tolerance and prevent tissue damage from immunopathology, via anti-inflammatory cytokines, inhibitor receptors and metabolic disruption. Here we show that Treg cells acquire an effector-like state, yet remain stable and functional, when exposed to interferon gamma (IFNγ) during infection with lymphocytic choriomeningitis and influenza A virus. Treg cell-restricted deletion of the IFNγ receptor (encoded by Ifngr1), but not the interleukin 12 (IL12) receptor (encoded by Il12rb2), prevented TH1-like polarization (decreased expression of T-bet, CXC motif chemokine receptor 3 and IFNγ) and promoted TH2-like polarization (increased expression of GATA-3, CCR4 and IL4). TH1-like Treg cells limited CD8+ T cell effector function, proliferation and memory formation during acute and chronic infection. These findings provide fundamental insights into how Treg cells sense inflammatory cues from the environment (such as IFNγ) during viral infection to provide guidance to the effector immune response. This regulatory circuit prevents prolonged immunoinflammatory responses and shapes the quality and quantity of the memory T cell response.

DOI: 10.1038/s41590-023-01453-w

Source: https://www.nature.com/articles/s41590-023-01453-w

Nature Immunology：《自然—免疫学》，创刊于2000年。隶属于施普林格·自然出版集团，最新IF：31.25
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