英国格拉斯哥大学Mariola Kurowska-Stolarska等研究人员合作发现，滑膜组织髓系树突状细胞亚群在健康和类风湿关节炎中表现出独特的组织生态位定位和功能。这一研究成果于2024年11月27日在线发表在国际学术期刊《免疫》上。

研究人员表示，目前的类风湿性关节炎（RA）治疗方法无法恢复免疫耐受性。研究人体滑膜组织（ST）中的树突状细胞（DC）群体可能揭示恢复RA免疫耐受性的途径。

通过对ST活检样本进行单细胞和空间转录组学分析，以及共培养系统，研究人员识别了具有不同功能的特定状态和生态位的DC群体。健康组织中含有耐受性较强的AXL⁺ DC2，位于滑膜层。活跃的RA中，增生的滑膜层充满了炎性DC3，这些细胞激活了CCL5阳性的效应记忆T细胞，促进了滑膜炎的发生。

在下层滑膜层中出现的淋巴样生态位富集了CCR7⁺ DC2，这些细胞与初始T细胞相互作用，可能驱动新效应T细胞的局部扩增。在缓解期，这些致病性生态位得到了消除，但耐受性DC2未能恢复，并且在病情复发之前，ST-DC3簇的血液前体被激活。靶向致病性DC3或恢复耐受性DC2可能有助于恢复RA关节中的免疫稳态。

附：英文原文

Title: Synovial tissue myeloid dendritic cell subsets exhibit distinct tissue-niche localization and function in health and rheumatoid arthritis

Author: Lucy MacDonald, Aziza Elmesmari, Domenico Somma, Jack Frew, Clara Di Mario, Roopa Madhu, Audrey Paoletti, Theodoros Simakou, Olympia M. Hardy, Barbara Tolusso, Denise Campobasso, Simone Perniola, Marco Gessi, Maria Rita Gigante, Luca Petricca, Dario Bruno, Lavinia Agra Coletto, Roberta Benvenuto, John D. Isaacs, Andrew Filby, David McDonald, Jasmine P.X. Sim, Nigel Jamieson, Kevin Wei, Maria Antonietta D’Agostino, Neal L. Millar, Simon Milling, Charles McSharry, Elisa Gremese, Karen Affleck, Kenneth F. Baker, Iain B. McInnes, Thomas D. Otto, Ilya Korsunsky, Stefano Alivernini, Mariola Kurowska-Stolarska

Issue&Volume: 2024-11-27

Abstract: Current rheumatoid arthritis (RA) treatments do not restore immune tolerance. Investigating dendritic cell (DC) populations in human synovial tissue (ST) may reveal pathways to reinstate tolerance in RA. Using single-cell and spatial transcriptomics of ST biopsies, as well as co-culture systems, we identified condition- and niche-specific DC clusters with distinct functions. Healthy tissue contained tolerogenic AXL+ DC2s in the lining niche. In active RA, the hyperplasic lining niche was populated with inflammatory DC3s that activated CCL5-positive effector memory T cells, promoting synovitis. Lymphoid niches that emerged in the sublining layer were enriched with CCR7+ DC2s, which interacted with naive T cells, potentially driving the local expansion of new effector T cells. Remission saw the resolution of these pathogenic niches but lacked recovery of tolerogenic DC2s and exhibited activation of blood precursors of ST-DC3 clusters prior to flare-ups. Targeting pathogenic DC3s or restoring tolerogenic DC2s may help restore immune homeostasis in RA joints.

DOI: 10.1016/j.immuni.2024.11.004

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00519-3