小柯机器人

瑞士巴塞尔大学Daniel D. Pinschewer，Anna-Friederike Marx和德国莱布尼茨研究所Max Löhning共同合作，近期取得重要工作进展。他们研究发现警报素白介素-33促进慢性病毒感染中Tcf-1⁺ CD8⁺ T细胞的增殖和稳定性维持。相关研究结果2023年2月20日在线发表于《免疫》杂志上。

据介绍，表达CD8⁺ T细胞的T细胞因子1（Tcf-1）表现出干细胞样的自我更新能力，使其成为抵抗慢性病毒感染和癌症的免疫防御关键。然而，促进这些干细胞样CD8⁺ T细胞（CD8⁺ SL）形成和维持的信号仍不明确。

通过对慢性病毒感染小鼠的CD8⁺ T细胞分化的研究，研究人员发现警报素白细胞介素33（IL-33）对CD8⁺SL的扩增和干样功能以及病毒 控制至关重要。IL-33受体（ST2）缺陷的CD8⁺ T细胞表现出偏向性的末端分化和Tcf-1的过早丢失。ST2缺陷的CD8⁺SL应答通过阻断I型干扰素信号恢复，表明IL-33平衡IFN-I效应以控制慢性感染中CD8⁺SL的形成。IL-33信号广泛增强了CD8⁺SL中染色质的可及性，并确定了这些细胞的再扩增潜力。

总之，这一研究确定IL-33-ST2轴是慢性病毒感染背景下重要的CD8+SL促进途径。

附：英文原文

Title: The alarmin interleukin-33 promotes the expansion and preserves the stemness of Tcf-1+ CD8+ T cells in chronic viral infection

Author: Anna-Friederike Marx, Sandra M. Kallert, Tobias M. Brunner, José A. Villegas, Florian Geier, Jonas Fixemer, Tiago Abreu-Mota, Peter Reuther, Weldy V. Bonilla, Jelizaveta Fadejeva, Mario Kreutzfeldt, Ingrid Wagner, Patricia Aparicio-Domingo, Leo Scarpellino, Mélanie Charmoy, Daniel T. Utzschneider, Claudia Hagedorn, Min Lu, Karen Cornille, Karsten Stauffer, Florian Kreppel, Doron Merkler, Dietmar Zehn, Werner Held, Sanjiv A. Luther, Max Lhning, Daniel D. Pinschewer

Issue&Volume: 2023-02-20

Abstract: T cell factor 1 (Tcf-1) expressing CD8+ T cells exhibit stem-like self-renewing capacity, rendering them key for immune defense against chronic viral infection and cancer. Yet, the signals that promote the formation and maintenance of these stem-like CD8+ T cells (CD8+SL) remain poorly defined.

Studying CD8+ T cell differentiation in mice with chronic viral infection, we identified the alarmin interleukin-33 (IL-33) as pivotal for the expansion and stem-like functioning of CD8+SL as well as for virus control. IL-33 receptor (ST2)-deficient CD8+ T cells exhibited biased end differentiation and premature loss of Tcf-1. ST2-deficient CD8+SL responses were restored by blockade of type I interferon signaling, suggesting that IL-33 balances IFN-I effects to control CD8+SL formation in chronic infection. IL-33 signals broadly augmented chromatin accessibility in CD8+SL and determined these cells’ re-expansion potential.

Our study identifies the IL-33-ST2 axis as an important CD8+SL-promoting pathway in the context of chronic viral infection.

DOI: 10.1016/j.immuni.2023.01.029

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00041-9

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