The alarmin interleukin-33在慢性病毒感染中促进了Tcf-1+CD8+T细胞的扩张和干细胞特性的保持。
The alarmin interleukin-33 promotes the expansion and preserves the stemness of Tcf-1+ CD8+ T cells in chronic viral infection.
发表日期：2023 Feb 14
作者：
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 Löhning, Daniel D Pinschewer
来源：
IMMUNITY
摘要：
T细胞因子1（Tcf-1）表达的CD8 + T细胞具有类似干细胞的自我更新能力，因此对于免疫防御慢性病毒性感染和癌症至关重要。然而，促进这些类似干细胞的CD8 + T细胞（CD8 + SL）的形成和维护的信号仍然定义不清。通过研究慢性病毒性感染的小鼠中的CD8 + T细胞分化，我们确定了警报因子白细胞介素-33（IL-33）对CD8 + SL的扩张和类干细胞功能以及病毒控制至关重要。ST2缺陷CD8 + T细胞展示出偏向性末端分化和Tcf-1的过早丧失。 ST2缺陷CD8 + SL反应通过阻断I型干扰素信号复苏，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信号广泛增加了CD8 + SL的染色质可及性，并决定这些细胞的再扩张潜力。我们的研究确定了IL-33-ST2轴作为慢性病毒性感染背景下重要的CD8 + SL促进途径。版权所有©2023作者。由Elsevier Inc.出版。保留所有权利。
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.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.