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Using single-cell spatial transcriptomics, RNA sequencing and ATAC sequencing of ~2,500,000 cells, we map 18 distinct stromal cell states within their cellular and cytokine signaling environments in human full-thickness CD bowel. Inflammatory fibroblasts (IFs) reside in immune cell-rich mucosal ulcers and are induced through combinatorial cytokine exposure suppressing submucosal universal fibroblast programs. The IF state is stabilized through transcription factor (TF) activity of GLI3, TWIST1, ETV4, PRDM1 and RELB, and does not spontaneously revert; however, histone deacetylase inhibition destabilizes the IF state, preventing IF secretome-induced epithelial transmigration and activation of neutrophils. The IF open chromatin configuration is distinct from that of fibrotic contractile stroma, which populate adjoining immune-depleted submucosal fibrotic niches. 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This has now been amended in the HTML and PDF versions of the article.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A.W. received grants\/research support\/speaker fees from: AbbVie, Alfasigma, Buhlmann, Bristol Meyers Squibb, Ferring, Galapagos, Helmsley trust, Janssen, Lilly, Pfizer, Takeda, Tillotts and Norman Collisson Foundation. S.P.T. received grants\/research support from: AbbVie, Celgene, Celsius, ECCO, Galapagos, GSK, Helmsley Trust, IOIBD, Janssen, Lilly, Pfizer, Takeda, UKIERI, Vifor, and Norman Collisson Foundation. Consulting Fees: Alimentiv; Apexian; Apollo; Arcturis; AstraZeneca; BMS; Clario; Cosmo; Endpoint Health; EQrX; Equillium; Ferring; Galapagos; Genentech\/Roche; Gilead; GSK; Janssen; Iterative Health; Lilly; Mestag; Microbiotica; ONO; Pfizer; Phesi; Protagonist; Sanofi; Satisfai; Sensyne Health; Spyre; Takeda; Teva; Theravance; Tr1X Bio\n                      ;\n                      Speaker fees: BMS, Ferring, GSK, Janssen, Lilly, Pfizer, Sun Pharma, Takeda. Share options: Satisfai Health. H.A.M. was a previous employee of UCB and AstraZeneca and currently holds a leadership or fiduciary role at Immunocore. He holds stock or stock options from Immunocore, GSK, UCB, BMS, Abbvie and J&J. T.T. is a current employee of J&J Innovative Medicine and holds stock in J&J. L.W.U. has received travel grants from Intuitive Surgical and holds a collaborative research grant from Boehringer Ingelheim. L.W.U. is currently affiliated with the Medical University of Vienna, Vienna, Austria. The research laboratory of U.O. was supported by Bayer Healthcare, Bristol Myers Squibb, GlaxoSmithKline and the Leducq Epigenetics in Atherosclerosis Network of the Leducq Foundation. P.K. has consulted for Biomunex, AZ, Infinitopes and UCB. S.A.T. is a scientific advisory board member of ForeSite Labs, OMass Therapeutics, QIAGEN, Xaira Therapeutics, a co-founder and equity holder of TransitionBio and Ensocell Therapeutics, a non-executive director of 10x Genomics and a part-time employee of GlaxoSmithKline. M.F. received speaker and\/or consultancy fees from Eli Lilly, UCB Pharma, Quell Therapeutics, Ono Pharma and received research funding from Eli Lilly and UCB. J.R. is a co-founder of Ground Truth Labs, Oxford and received funding from Novo Nordisk. The other authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}