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

IF 27.7 1区 医学 Q1 IMMUNOLOGY Nature Immunology Pub Date : 2024-10-22 DOI:10.1038/s41590-024-01994-8
Tom Thomas, Matthias Friedrich, Charlotte Rich-Griffin, Mathilde Pohin, Devika Agarwal, Julia Pakpoor, Carl Lee, Ruchi Tandon, Aniko Rendek, Dominik Aschenbrenner, Ashwin Jainarayanan, Alexandru Voda, Jacqueline H. Y. Siu, Raphael Sanches-Peres, Eloise Nee, Dharshan Sathananthan, Dylan Kotliar, Peter Todd, Maria Kiourlappou, Lisa Gartner, Nicholas Ilott, Fadi Issa, Joanna Hester, Jason Turner, Saba Nayar, Jonas Mackerodt, Fan Zhang, Anna Jonsson, Michael Brenner, Soumya Raychaudhuri, Ruth Kulicke, Danielle Ramsdell, Nicolas Stransky, Ray Pagliarini, Piotr Bielecki, Noah Spies, Brian Marsden, Stephen Taylor, Allon Wagner, Paul Klenerman, Alissa Walsh, Mark Coles, Luke Jostins-Dean, Fiona M. Powrie, Andrew Filer, Simon Travis, Holm H. Uhlig, Calliope A. Dendrou, Christopher D. Buckley
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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. In this Resource, Buckley and colleagues profile patients with Crohn’s disease and ulcerative colitis before and after adalimumab therapy. Specific pretreatment differences in the epithelial and myeloid compartments were associated with remission outcomes in both diseases. The authors also describe the cellular circuitry in nonremission patients following treatment.

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炎症性肠病抗肿瘤坏死因子治疗纵向单细胞图谱
免疫介导的炎症性疾病(IMIDs)的精准医疗需要从细胞角度了解治疗反应。我们描述了克罗恩病(CD)和溃疡性结肠炎(UC)在阿达木单抗(一种抗肿瘤坏死因子(anti-TNF))治疗后的治疗图谱。我们从 216 份肠道活检样本(41 名受试者)中生成了约 100 万个单细胞转录组,分为 109 种细胞状态,揭示了疾病的特异性差异。系统生物学空间分析确定了 CD 的肉芽肿特征,以及 CD 和 UC 的 T 细胞聚集和上皮损伤的干扰素 (IFN) 反应特征。上皮细胞和骨髓细胞治疗前的差异与这两种疾病的缓解结果有关。纵向比较显示了非缓解期的疾病进展:CD 病的髓细胞和 T 细胞紊乱以及 UC 病的多细胞 IFN 信号增加。在类风湿性关节炎(RA)滑膜中也观察到了淋巴细胞病理型的 IFN 信号。我们的治疗图谱代表了多种炎症性疾病中最常见的生物治疗方法--抗肿瘤坏死因子(anti-TNF)--所造成的最大的细胞干扰普查。
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来源期刊
Nature Immunology
Nature Immunology 医学-免疫学
CiteScore
40.00
自引率
2.30%
发文量
248
审稿时长
4-8 weeks
期刊介绍: Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.
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