{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:02:29Z","timestamp":1790344949550,"version":"4.1.0"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ulcerative colitis (UC) is a chronic mucosal immune disorder in which 30-50% of patients fail biologic therapy, yet the full-thickness immune architecture of medically refractory disease and reliable tissue-level markers of treatment response remain undefined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using 10x Visium HD spatial transcriptomics (16-\u00b5m bins; 615,274 bins), we generated a full-thickness spatial atlas of surgically resected colon from patients with medically refractory UC (n=3) and controls (n=3), integrating niche-stratified differential expression, spatial cell\u2013cell communication, SCENIC regulon inference and single-sample GSEA with immunofluorescence and DSS-colitis flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We resolved 18 spatial immune\u2013stromal niches across five tissue modules. At the mucosal frontline, epithelial barrier collapse was accompanied by a 20-fold expansion of ulcer-bed stroma (p=0.030) that co-localised with an Acute Neutrophil Niche and was associated with neutrophil recruitment via CXCL12\u2013CXCR4 signalling, forming a spatially integrated ulcerogenic unit. In the submucosa, a humoral immune programme was associated with tertiary lymphoid structures (TLS) and plasma-cell survival-related signalling (MIF\u2013CD74 and LTB\u2013CD40). This niche architecture was immunologically informative: an Acute Neutrophil Niche signature was enriched in biologic non-responders across six adult cohorts (AUC 0.67\u20130.99) and in non-remission patients of the paediatric PROTECT cohort, and a five-niche model showed discriminative performance in adult cohorts across independent datasets and drug classes (anti-TNF and anti-integrin; cross-cohort AUC 0.68\u20130.97), although this performance did not transfer to the paediatric cohort (AUC \u2248 0.51\u20130.62). Expansion of TNFAIP2+ TLS-resident B cells was confirmed at the protein\u00a0level\u00a0in a DSS colitis mouse model by immunofluorescence and flow cytometry (p=0.0079).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Together, this full-thickness atlas defines the spatial immune ecosystem of refractory UC \u2013 neutrophil niches, TLS and plasma-cell survival programmes \u2013 and yields cellular-niche signatures reproducibly associated with treatment outcome across drug classes, providing an immunologically grounded framework that may inform biologic selection, pending prospective validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1929046","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:25:14Z","timestamp":1790342714000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A full-thickness spatial transcriptomics atlas of medically refractory ulcerative colitis identifies niche signatures associated with biologic non-response"],"prefix":"10.3389","volume":"17","author":[{"given":"Qingquan","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Centre Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University","place":["Ningbo, China"]},{"name":"Department of Hepatology and Gastroenterology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Campus Virchow-Klinikum and Campus Charit\u00e9 Mitte","place":["Berlin, 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