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在适应性耐受过程中，干扰素-γ和白细胞介素-27正向调节1型调节性T细胞的发育。

Interferon-γ and IL-27 positively regulate type 1 regulatory T cell development during adaptive tolerance.

作者信息

Lecky David A J, Sheriff Lozan, Rouvray Sophie T, George Lorna S, Copland Alastair, Drummond Rebecca A, Wraith David C, Bending David

机构信息

Department of Immunology and Immunotherapy, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK.

出版信息

iScience. 2025 Mar 28;28(5):112308. doi: 10.1016/j.isci.2025.112308. eCollection 2025 May 16.

DOI:10.1016/j.isci.2025.112308
PMID:40276760
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12018090/
Abstract

Strong T cell receptor (TCR) and interleukin (IL)-27 signaling influence type 1 regulatory (Tr1) T cell development, but whether other signals determine their differentiation is unclear. Utilizing Tg4 TCR transgenic mice, we established a model for rapid Tr1 cell induction. A single high dose of [4Y]-MBP peptide drove the differentiation of T cells with Tr1 cell mRNA and protein signatures. Kinetic transcriptional and phenotypic analyses revealed that the Tr1 cell module was transient and preceded by transcription in other CD4 T cells. Changes in Tr1 cell frequency correlated with altered macrophage activation, while neutralization of interferon (IFN)γ reduced Tr1 cell frequency and the TCR signal strength markers Nur77, inducible T cell costimulator (ICOS), and OX40. Antibody depletion experiments inferred that the relevant source of IFNγ was not natural killer (NK) cell derived. Additionally, blocking IL-27 in combination with IFNγ neutralization additively reduced Tr1 cell frequency . These findings reveal that IFNγ has a non-redundant role in augmenting Tr1 cell differentiation .

摘要

强T细胞受体（TCR）和白细胞介素（IL）-27信号传导影响1型调节性（Tr1）T细胞的发育，但其他信号是否决定其分化尚不清楚。利用Tg4 TCR转基因小鼠，我们建立了一个快速诱导Tr1细胞的模型。单次高剂量的[4Y]-髓鞘碱性蛋白（MBP）肽驱动具有Tr1细胞mRNA和蛋白质特征的T细胞分化。动力学转录和表型分析表明，Tr1细胞模块是短暂的，且先于其他CD4 T细胞中的转录过程。Tr1细胞频率的变化与巨噬细胞活化的改变相关，而干扰素（IFN）γ的中和降低了Tr1细胞频率以及TCR信号强度标志物Nur77、诱导性T细胞共刺激分子（ICOS）和OX40。抗体清除实验推断，IFNγ的相关来源不是自然杀伤（NK）细胞衍生的。此外，联合阻断IL-27与中和IFNγ可累加性降低Tr1细胞频率。这些发现揭示了IFNγ在增强Tr1细胞分化中具有不可替代的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cca/12018090/dd2fdff3835f/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cca/12018090/a2abdfb63f5a/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cca/12018090/82b57ef28040/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cca/12018090/d26c648739a4/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cca/12018090/7b65b28d5127/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cca/12018090/552de0437edb/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cca/12018090/dd2fdff3835f/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cca/12018090/a2abdfb63f5a/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cca/12018090/82b57ef28040/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cca/12018090/d26c648739a4/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cca/12018090/7b65b28d5127/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cca/12018090/552de0437edb/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cca/12018090/dd2fdff3835f/gr5.jpg

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