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.

免疫介导的炎症性疾病 （IMID） 的精准医学需要细胞对治疗反应的理解。我们描述了抗肿瘤坏死因子 （anti-TNF） 治疗阿达木单抗后克罗恩病 （CD） 和溃疡性结肠炎 （UC） 的治疗图谱。我们从 216 个肠道活检 （41 名受试者） 中生成了 ~100 万个单细胞转录组，分为 109 个细胞状态，揭示了疾病特异性差异。一项系统生物学空间分析确定了 CD 中的肉芽肿特征和定位于 CD 和 UC 中 T 细胞聚集体和上皮损伤的干扰素 （IFN） 反应特征。上皮和髓系隔室的治疗前差异与两种疾病的缓解结局相关。纵向比较显示未缓解时的疾病进展： CD 中骨髓和 T 细胞扰动，UC 中多细胞 IFN 信号增加。在具有淋巴病理型的类风湿性关节炎 （RA） 滑膜中也观察到 IFN 信号传导。我们的治疗图谱代表了对多种炎症性疾病中最常见的生物治疗抗 TNF 的扰动的最大细胞普查。