{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:54:55Z","timestamp":1790747695424,"version":"4.1.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"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>Atopic dermatitis (AD) is a common chronic inflammatory disorder of the skin. Despite the availability of targeted biologics like dupilumab, heterogeneous treatment responses persist, highlighting the need for reliable biomarkers and a deeper understanding of cell-type-associated molecular programs within the tissue microenvironment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This exploratory study integrated public microarray, single-cell RNA sequencing, and spatial transcriptomic datasets. GSE130588, comprising 124 lesional AD skin samples, was used for weighted gene co-expression network analysis (WGCNA). GSE59294 comprised 40 skin biopsies from 18 patients, including 16 pre-treatment lesional, 12 post-treatment lesional, 7 pre-treatment non-lesional, and 5 post-treatment non-lesional samples, and was used for differential expression analysis. The single-cell query cohort comprised 66,846 cells from 25 samples, with downstream analyses restricted to 19 blister-derived samples. Regulon activity was computationally inferred. GSE197023 comprised 20 spatial transcriptomic samples, including 7 lesional AD, 7 non-lesional AD, and 6 healthy-control samples, and was analyzed using cell-population deconvolution. CCR7 immunoreactivity was assessed by immunohistochemistry in independent healthy-control and lesional AD skin samples (\n                      <jats:italic>n<\/jats:italic>\n                      = 5 per group) analyze.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      WGCNA identified disease-severity-associated gene modules enriched in immune and cell-cycle-related processes. Nominal-\n                      <jats:italic>P<\/jats:italic>\n                      -value-based integration with differential expression results identified seven exploratory candidate hub genes (GZMB, CCR7, GPR183, MMP12, IL7R, RGS1, and KLHDC7B) associated with immune- cell abundance patterns. FDR-adjusted sensitivity analysis supported MMP12 and RGS1 in the lesional-versus-non-lesional comparison, whereas none of the seven genes reached nominal or FDR-adjusted significance in the paired treatment analysis. Single-cell reference mapping showed cell-type-associated expression of GZMB in cytotoxic T-cell populations and\n                      <jats:italic>CCR7<\/jats:italic>\n                      and\n                      <jats:italic>MMP12<\/jats:italic>\n                      in dendritic-cell subsets. Computational regulon analysis identified candidate cell-type-associated regulatory signals and differences in inferred regulon activity across treatment-state groups. Spatial deconvolution indicated predominantly dermal distributions of inferred immune-cell populations. Immunohistochemical assessment showed higher relative CCR7 immunoreactivity in lesional AD skin than in healthy-control skin.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These cross-modal analyses linked candidate molecular signals todendritic-cell- and T- cell-associated patterns in AD. These findings are exploratory and hypothesis-generating and do not establish validated biomarkers, causal regulatory mechanisms, or predictors of treatment response. Independent cohort replication and functional and cell-type-specific validation are required.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1863607","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:56:35Z","timestamp":1790744195000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integration of bulk and single-cell transcriptomics with spatial analysis identifies candidate hub genes and inferred regulatory programs in atopic dermatitis"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuqiao","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, Anhui, China"]},{"name":"Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education","place":["Hefei, Anhui, China"]},{"name":"Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province","place":["Hefei, Anhui, China"]},{"name":"The School of Management, Soonchunhyang University","place":["Asan-si, Chungcheongnam-do, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulong","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, Anhui, China"]},{"name":"Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education","place":["Hefei, Anhui, China"]},{"name":"Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, Anhui, China"]},{"name":"Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education","place":["Hefei, Anhui, China"]},{"name":"Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Metabolic Disease Research Center, School of Basic Medicine, Anhui Medical University","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengxiu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, Anhui, China"]},{"name":"Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education","place":["Hefei, Anhui, China"]},{"name":"Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province","place":["Hefei, Anhui, 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