英国牛津大学Christopher D. Buckley等研究人员，合作绘制出抗肿瘤坏死因子治疗炎症性肠病的纵向单细胞图谱。相关论文于2024年10月22日在线发表在《自然—免疫学》杂志上。

研究人员描述了在接受抗肿瘤坏死因子（anti-TNF）治疗的克罗恩病（CD）和溃疡性结肠炎（UC）患者中建立的治疗图谱。研究人员从216个肠道活检样本（41名受试者）生成了约100万个单细胞转录组，并组织成109种细胞状态，揭示了疾病特异性差异。

系统生物学空间分析识别了CD中的肉芽肿特征，以及UC和CD中T细胞聚集和上皮损伤的干扰素（IFN）反应特征。预处理时上皮和髓系组分的差异与两种疾病的缓解结果相关。纵向比较显示非缓解患者的疾病进展：CD中的髓系和T细胞扰动以及UC中增加的多细胞IFN信号传导。

在类风湿性关节炎（RA）滑膜中，也观察到了具有淋巴样病理特征的IFN信号。这一治疗图谱代表了在多种炎症性疾病中接受最常见的生物治疗——抗TNF治疗的细胞扰动的最大细胞普查。

据了解，精准医学在免疫介导的炎症性疾病（IMID）中需要对治疗反应的细胞理解。

附：英文原文

Title: A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease

Author: Thomas, Tom, Friedrich, Matthias, Rich-Griffin, Charlotte, Pohin, Mathilde, Agarwal, Devika, Pakpoor, Julia, Lee, Carl, Tandon, Ruchi, Rendek, Aniko, Aschenbrenner, Dominik, Jainarayanan, Ashwin, Voda, Alexandru, Siu, Jacqueline H. Y., Sanches-Peres, Raphael, Nee, Eloise, Sathananthan, Dharshan, Kotliar, Dylan, Todd, Peter, Kiourlappou, Maria, Gartner, Lisa, Ilott, Nicholas, Issa, Fadi, Hester, Joanna, Turner, Jason, Nayar, Saba, Mackerodt, Jonas, Zhang, Fan, Jonsson, Anna, Brenner, Michael, Raychaudhuri, Soumya, Kulicke, Ruth, Ramsdell, Danielle, Stransky, Nicolas, Pagliarini, Ray, Bielecki, Piotr, Spies, Noah, Marsden, Brian, Taylor, Stephen, Wagner, Allon, Klenerman, Paul, Walsh, Alissa, Coles, Mark, Jostins-Dean, Luke, Powrie, Fiona M., Filer, Andrew, Travis, Simon, Uhlig, Holm H., Dendrou, Calliope A., Buckley, Christopher D.

Issue&Volume: 2024-10-22

Abstract: Precision medicine in immune-mediated inflammatory diseases (IMIDs) requires a cellular understanding of treatment response. We describe a therapeutic atlas for Crohn’s disease (CD) and ulcerative colitis (UC) following adalimumab, an anti-tumour necrosis factor (anti-TNF) treatment. We generated ~1 million single-cell transcriptomes, organised into 109 cell states, from 216 gut biopsies (41 subjects), revealing disease-specific differences. A systems biology-spatial analysis identified granuloma signatures in CD and interferon (IFN)-response signatures localising to T cell aggregates and epithelial damage in CD and UC. Pretreatment differences in epithelial and myeloid compartments were associated with remission outcomes in both diseases. Longitudinal comparisons demonstrated disease progression in nonremission: myeloid and T cell perturbations in CD and increased multi-cellular IFN signalling in UC. IFN signalling was also observed in rheumatoid arthritis (RA) synovium with a lymphoid pathotype. Our therapeutic atlas represents the largest cellular census of perturbation with the most common biologic treatment, anti-TNF, across multiple inflammatory diseases.

DOI: 10.1038/s41590-024-01994-8

Source: https://www.nature.com/articles/s41590-024-01994-8