{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:32:26Z","timestamp":1791930746044,"version":"4.3.4"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"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>Allergic rhinitis (AR) is a common chronic nasal mucosal inflammatory disorder driven by type 2 immunity, but the spatial stromal\u2013immune cell interactions underlying its pathogenesis remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used 10x Genomics Xenium\n                      <jats:italic>In Situ<\/jats:italic>\n                      spatial transcriptomics to map the nasal mucosa of 10 AR patients and 10 non-allergic controls, combined with unsupervised cell clustering, differential gene expression (DE) analysis of COL1A1\n                      <jats:sup>+<\/jats:sup>\n                      PDGFRA\n                      <jats:sup>+<\/jats:sup>\n                      fibroblasts, qRT-PCR validation, ligand\u2013receptor modeling (CellPhoneDB\/NicheNet), and multimodal integration of spatial, transcriptional, and clinical data.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Nine major cell types with tissue-specific localization were identified. The AR samples showed expanded fibroblast-rich regions (34.2 \u00b1 3.1% vs. 15.6 \u00b1 2.4% in controls;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001) and increased adjacency between CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells and fibroblasts (62.3 \u00b1 4.5% vs. 28.7 \u00b1 3.8% in controls;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001). The fibroblasts in AR had 187 upregulated genes (e.g., TSLP, IL33) that were spatially enriched near CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells and validated by qRT-PCR. CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells within 20 \u03bcm of fibroblasts in AR showed higher Th2 cytokine expression (IL4, IL5, IL13) and Th2\/GATA3 signature scores (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001). Three key ligand\u2013receptor axes (TSLP\u2013IL7R, OX40L\u2013OX40, and ICOSL\u2013ICOS) drove the fibroblast\u2013Th2 crosstalk. A \u201cfibroblast\u2013T cell crosstalk score\u201d was \u00d74.8 higher in AR (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001) and correlated with clinical severity (serum IgE:\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0=\u00a00.71; SPT wheal diameter:\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0=\u00a00.65;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>AR is defined by expanded fibroblast niches, fibroblast-derived type 2 mediators, and ligand\u2013receptor-dependent fibroblast\u2013Th2 crosstalk\u2014a central pathogenic driver and potential therapeutic target.<\/jats:p>\n                  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