biostudies-literatureMartin JCSanford J. Grossman Charitable TrustFondation Bettencourt-SchuellerPhilippe FoundationNIDDK NIH HHSNIAID NIH HHSCrohn's & Colitis FoundationCrohn's and Colitis FoundationNCI NIH HHSNIHNIH HHSBoehringer Ingelheim Pharmaceuticals1493-1508.e20https://www.ebi.ac.uk/biostudies/studies/S-EPMC7060942biostudies-literatureUnknown178(6)Clinical benefits of cytokine blockade in ileal Crohn's disease (iCD) are limited to a subset of patients. Here, we applied single-cell technologies to iCD lesions to address whether cellular heterogeneity contributes to treatment resistance. We found that a subset of patients expressed a unique cellular module in inflamed tissues that consisted of IgG plasma cells, inflammatory mononuclear phagocytes, activated T cells, and stromal cells, which we named the GIMATS module. Analysis of ligand-receptor interaction pairs identified a distinct network connectivity that likely drives the GIMATS module. Strikingly, the GIMATS module was also present in a subset of patients in four independent iCD cohorts (n = 441), and its presence at diagnosis correlated with failure to achieve durable corticosCellSingle-Cell Analysis of Crohn's Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy.PMC7060942U24 CA224319S10 OD023547-01U24 DK062429R56AI137244U19 AI128949558865S10 OD018522292052R01 DK106593U01 DK062422K23 DK111995U24 AI118644274356U01 DK062429R56 AI137244R01 CA190400419130K23KD111995-01A1S10 OD023547T32 CA0782071878Ungaro RChuang LSGiri MMartin JCMerad MSalmon HBoschetti GDenson LAKugathasan SMbow MLFine JSHyams JSAkturk GCho JHKenigsberg EGreenstein AJChang CGrout JAWalker LDesai PTNayar SWhitehurst CEGnjatic SRahman AHLeader ASchadt EEKo HMLaface IFriedman JRGettler KDubinsky MfalseSingle-Cell Analysis of Crohn's Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy.Clinical benefits of cytokine blockade in ileal Crohn's disease (iCD) are limited to a subset of patients. Here, we applied single-cell technologies to iCD lesions to address whether cellular heterogeneity contributes to treatment resistance. We found that a subset of patients expressed a unique cellular module in inflamed tissues that consisted of IgG plasma cells, inflammatory mononuclear phagocytes, activated T cells, and stromal cells, which we named the GIMATS module. Analysis of ligand-receptor interaction pairs identified a distinct network connectivity that likely drives the GIMATS module. Strikingly, the GIMATS module was also present in a subset of patients in four independent iCD cohorts (n = 441), and its presence at diagnosis correlated with failure to achieve durable corticos2019-01-01T00:00:00Z2019 Sep2026-05-04T08:38:15.921Z2020-10-29T14:21:52ZS-EPMC70609423147437010.1016/j.cell.2019.08.008