Heim Taylor A, Lin Ziyan, Steele Maria M, Mudianto Tenny, Lund Amanda W
Ronald O. Perelman Department of Dermatology, NYU Grossman School of Medicine, New York, NY, USA.
Applied Bioinformatics Laboratories, NYU Langone Health, New York, NY, USA.
bioRxiv. 2023 Feb 15:2023.02.14.528487. doi: 10.1101/2023.02.14.528487.
Tissue resident memory T cells (T) provide important protection against infection, and yet the interstitial signals necessary for their formation and persistence remain incompletely understood. Here we show that antigen-dependent induction of the chemokine receptor, CXCR6, is a conserved requirement for T formation in peripheral tissue after viral infection. CXCR6 was dispensable for the early accumulation of antigen-specific CD8 T cells in skin and did not restrain their exit. Single cell sequencing indicated that CXCR6 CD8 T cells were also competent to acquire a transcriptional program of residence but exhibited deficiency in multiple pathways that converged on survival and metabolic signals necessary for memory. As such, CXCR6 CD8 T cells exhibited increased rates of apoptosis relative to controls in the dermis, leading to inefficient T formation. CXCR6 expression may therefore represent a common mechanism across peripheral non-lymphoid tissues and inflammatory states that increases the probability of long-term residence.
组织驻留记忆T细胞（T细胞）为抵御感染提供了重要保护，然而其形成和维持所必需的间质信号仍未被完全理解。在这里，我们表明趋化因子受体CXCR6的抗原依赖性诱导是病毒感染后外周组织中T细胞形成的一个保守要求。CXCR6对于抗原特异性CD8 T细胞在皮肤中的早期积累并非必需，并且不会限制它们的迁出。单细胞测序表明，CXCR6+ CD8 T细胞也有能力获得驻留的转录程序，但在多个汇聚于记忆所必需的存活和代谢信号的途径中表现出缺陷。因此，相对于真皮中的对照，CXCR6+ CD8 T细胞表现出更高的凋亡率，导致T细胞形成效率低下。因此，CXCR6的表达可能代表了外周非淋巴组织和炎症状态中的一种共同机制，这种机制增加了长期驻留的可能性。
