Strobl Johanna, Pandey Ram Vinay, Krausgruber Thomas, Bayer Nadine, Kleissl Lisa, Reininger Bärbel, Vieyra-Garcia Pablo, Wolf Peter, Jentus Maaia-Margo, Mitterbauer Margit, Wohlfarth Philipp, Rabitsch Werner, Stingl Georg, Bock Christoph, Stary Georg
Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria.
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
Sci Transl Med. 2020 Nov 18;12(570). doi: 10.1126/scitranslmed.abb7028.
The skin contains a population of tissue-resident memory T cells (T) that is thought to contribute to local tissue homeostasis and protection against environmental injuries. Although information about the regulation, survival program, and pathophysiological roles of T has been obtained from murine studies, little is known about the biology of human cutaneous T Here, we showed that host-derived CD69 αβ memory T cell clones in the epidermis and dermis remain stable and functionally competent for at least 10 years in patients with allogeneic hematopoietic stem cell transplantation. Single-cell RNA sequencing revealed low expression of genes encoding tissue egress molecules by long-term persisting T in the skin, whereas tissue retention molecules and stem cell markers were displayed by T The transcription factor RUNX3 and the surface molecule galectin-3 were preferentially expressed by host T cells at the RNA and protein levels, suggesting two new markers for human skin T Furthermore, skin lesions from patients developing graft-versus-host disease (GVHD) showed a large number of cytokine-producing host-derived T, suggesting a contribution of these cells to the pathogenesis of GVHD. Together, our studies highlighted the relationship between the local human skin environment and long-term persisting T, which differs from murine skin. Our results also indicated that local tissue inflammation occurs through host-derived T after allogeneic hematopoietic stem cell transplantation.
皮肤中含有一群组织驻留记忆T细胞（T细胞），人们认为它们有助于维持局部组织稳态并抵御环境损伤。尽管已经从小鼠研究中获得了有关T细胞的调节、存活程序和病理生理作用的信息，但对于人类皮肤T细胞的生物学特性却知之甚少。在此，我们表明，在异基因造血干细胞移植患者中，表皮和真皮中宿主来源的CD69αβ记忆T细胞克隆至少10年保持稳定且功能正常。单细胞RNA测序显示，皮肤中长期存在的T细胞编码组织逸出分子的基因表达较低，而T细胞则显示出组织保留分子和干细胞标志物。转录因子RUNX3和表面分子半乳糖凝集素-3在RNA和蛋白质水平上优先由宿主T细胞表达，提示它们是人类皮肤T细胞的两个新标志物。此外，发生移植物抗宿主病（GVHD）患者的皮肤病变显示大量产生细胞因子的宿主来源T细胞，表明这些细胞对GVHD的发病机制有贡献。总之，我们的研究突出了人类局部皮肤环境与长期存在的T细胞之间的关系，这与小鼠皮肤不同。我们的结果还表明，异基因造血干细胞移植后，局部组织炎症是通过宿主来源的T细胞发生的。
