Murine gamma delta intraepithelial lymphocyte response to type I IFN and TCR blockade

Interferon alpha (IFNa) is a pro-inflammatory cytokine that is rapidly upregulated as part of an innate immune response. Gamma delta intraepithelial lymphocytes (gd IEL) mount a rapid antimicrobial response to luminal microorganisms and previous report indicate that the T cell receptor (TCR) of these cells is constantly triggered at steady-state. We assessed the contribution of tonic TCR activation in response to acute, systemic IFNa administration among murine gd IELs. Our data demonstrate that inhibiting basal TCR signaling has a minimal effect on the transcriptional profile of gd IELs and acute IFNa exposure induces antiviral gene programs independent of TCR signaling. Overall design: Mice were treated mice with 200 ug TCRgd antibody (UC7-13D5) or Armenian hamster IgG i.p. (-48 or -24 h) prior to i.v. administration with 1 ug murine IFNa or phosphate buffered saline (PBS) for 5 h. RNAseq was performed on sorted gd IELs isolated from murine small intestine from each of the following treatment groups: IgG-PBS, IgG-IFNa, UC713D5-PBS, UC713D5-IFNa

α干扰素（Interferon alpha, IFNa）是一种促炎细胞因子，作为固有免疫应答的组成部分会被快速上调。γδ上皮内淋巴细胞（Gamma delta intraepithelial lymphocytes, gd IEL）可对腔道微生物产生快速抗菌应答，既往研究表明，这类细胞的T细胞受体（T cell receptor, TCR）在稳态下会持续受到激活。本研究评估了基础TCR活化对小鼠γδ上皮内淋巴细胞在接受急性全身性α干扰素给药后的应答贡献。我们的实验数据显示，抑制基础TCR信号通路对γδ上皮内淋巴细胞的转录谱仅产生极微弱的影响，而急性α干扰素暴露可诱导不依赖于TCR信号通路的抗病毒基因程序。

实验整体设计：实验小鼠于静脉注射1 μg小鼠α干扰素或磷酸盐缓冲液（PBS）并持续处理5小时前，分别在-48小时或-24小时接受腹腔注射200 μg TCRγδ抗体（UC7-13D5）或叙利亚仓鼠IgG。从以下四个处理组的小鼠小肠中分离分选得到γδ上皮内淋巴细胞，并对其进行RNA测序：IgG-PBS组、IgG-IFNa组、UC713D5-PBS组、UC713D5-IFNa组