德国莱布尼茨免疫治疗研究所Markus Feuerer团队在研究中取得进展。他们揭示了DNA低甲基化特征定义了皮肤组织中的人类调节性T细胞，并识别了它们的血液循环对应体。这一研究成果发表在2025年7月16日出版的国际学术期刊《自然—免疫学》上。

该课题组人员对来自皮肤和血液的人类T_reg细胞进行了全基因组DNA甲基化分析，并将这些数据整合到多组学框架中，包括染色质可及性和基因表达。该分析确定了控制皮肤Tr_eg细胞组织适应性的程序。该课题组研究人员发现转座因子亚家族代表了组织T_reg细胞低甲基化景观的主要组成部分。基于T细胞抗原受体序列和DNA低甲基化同源性，他们的数据表明血液CCR8⁺ T_reg细胞含有再循环的人类皮肤T_reg细胞。相反，染色质可及性和基因表达的差异表明在再循环过程中组织适应程序的某种逆转。他们的发现提供了对人体组织T_reg细胞生物学的见解，这可能有助于利用这些细胞用于治疗目的。

研究人员表示，CD4⁺调节性T （T_reg）细胞在组织中发挥重要的免疫调节和再生作用。尽管它们很重要，但人类组织T_reg细胞的表观遗传学和分化尚未完全了解。

附：英文原文

Title: DNA hypomethylation traits define human regulatory T cells in cutaneous tissue and identify their blood recirculating counterparts

Author: Beumer, Niklas, Imbusch, Charles D., Kaufmann, Tamara, Schmidleithner, Lisa, Gtter, Kathrin, Stve, Philipp, Marchel, Harriet, Weichenhan, Dieter, Bhr, Marion, Ruhland, Brigitte, Marini, Federico, Sanderink, Lieke, Ritter, Uwe, Simon, Malte, Braband, Kathrin Luise, Voss, Morten Michael, Helbich, Sara Salome, Mihoc, Delia Mihaela, Hotz-Wagenblatt, Agnes, Nassabi, Hadrian, Eigenberger, Andreas, Prantl, Lukas, Gebhard, Claudia, Rehli, Michael, Strieder, Nicholas, Singh, Kartikeya, Schmidl, Christian, Plass, Christoph, Huehn, Jochen, Hehlgans, Thomas, Polansky, Julia K., Brors, Benedikt, Delacher, Michael, Feuerer, Markus

Issue&Volume: 2025-07-16

Abstract: CD4+ regulatory T (Treg) cells in tissues play crucial immunoregulatory and regenerative roles. Despite their importance, the epigenetics and differentiation of human tissue Treg cells are incompletely understood. Here, we performed genome-wide DNA methylation analysis of human Treg cells from skin and blood and integrated these data into a multiomic framework, including chromatin accessibility and gene expression. This analysis identified programs that governed the tissue adaptation of skin Treg cells. We found that subfamilies of transposable elements represented a major constituent of the hypomethylated landscape in tissue Treg cells. Based on T cell antigen receptor sequence and DNA hypomethylation homologies, our data indicate that blood CCR8+ Treg cells contain recirculating human skin Treg cells. Conversely, differences in chromatin accessibility and gene expression suggest a certain reversal of the tissue adaptation program during recirculation. Our findings provide insights into the biology of human tissue Treg cells, which may help harness these cells for therapeutic purposes.

DOI: 10.1038/s41590-025-02210-x

Source: https://www.nature.com/articles/s41590-025-02210-x