{"doi":"10.1038/s41467-022-35319-w","title":"Spatial transcriptomics landscape of lesions from non-communicable inflammatory skin diseases","abstract":"Abundant heterogeneous immune cells infiltrate lesions in chronic inflammatory diseases and characterization of these cells is needed to distinguish disease-promoting from bystander immune cells. Here, we investigate the landscape of non-communicable inflammatory skin diseases (ncISD) by spatial transcriptomics resulting in a large repository of 62,000 spatially defined human cutaneous transcriptomes from 31 patients. Despite the expected immune cell infiltration, we observe rather low numbers of pathogenic disease promoting cytokine transcripts (IFNG, IL13 and IL17A), i.e. >125 times less compared to the mean expression of all other genes over lesional skin sections. Nevertheless, cytokine expression is limited to lesional skin and presented in a disease-specific pattern. Leveraging a density-based spatial clustering method, we identify specific responder gene signatures in direct proximity of cytokines, and confirm that detected cytokine transcripts initiate amplification cascades of up to thousands of specific responder transcripts forming localized epidermal clusters. Thus, within the abundant and heterogeneous infiltrates of ncISD, only a low number of cytokine transcripts and their translated proteins promote disease by initiating an inflammatory amplification cascade in their local microenvironment.","journal":"Nature Communications","year":2022,"id":5005,"datarank":2.2201652763111386,"base_score":4.290459441148391,"endowment":4.290459441148391,"self_citation_contribution":0.6435689161722588,"citation_network_contribution":1.5765963601388797,"self_endowment_contribution":0.6435689161722588,"citer_contribution":1.5765963601388797,"corpus_percentile":65.41903986981285,"corpus_rank":426,"citation_count":85,"citer_count":74,"citers_with_citation_signal":55,"citers_with_endowment":55,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.806,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-12-13","fair_score":49.7917,"fair_percentile":77.9023746701847,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1586,"name":"M. Mubarak","orcid":null,"position":2,"is_corresponding":false},{"id":1581,"name":"A. Farnoud","orcid":null,"position":4,"is_corresponding":false},{"id":1583,"name":"E. Scala","orcid":null,"position":5,"is_corresponding":false},{"id":51175,"name":"Nils Kurzen","orcid":"0000-0001-7939-3983","position":6,"is_corresponding":false},{"id":51176,"name":"A. C. Pilz","orcid":null,"position":7,"is_corresponding":false},{"id":1602,"name":"Nayanika Bhalla","orcid":"0000-0002-6800-0432","position":8,"is_corresponding":false},{"id":1588,"name":"M. Stahle","orcid":null,"position":10,"is_corresponding":false},{"id":1252,"name":"Tilo Biedermann","orcid":"0000-0002-5352-5105","position":11,"is_corresponding":false},{"id":1253,"name":"Carsten B. Schmidt‐Weber","orcid":"0000-0002-3203-8084","position":12,"is_corresponding":false},{"id":42,"name":"Fabian Joachim Theis","orcid":"0000-0002-2419-1943","position":13,"is_corresponding":false},{"id":1605,"name":"Michael P. Menden","orcid":"0000-0003-0267-5792","position":16,"is_corresponding":false},{"id":1256,"name":"Stefanie  Eyerich","orcid":"0000-0002-1166-2355","position":17,"is_corresponding":false},{"id":1597,"name":"Christina Hillig","orcid":"0000-0001-7447-547X","position":18,"is_corresponding":false},{"id":1603,"name":"Mohammad S. Mubarak","orcid":"0000-0002-9782-0835","position":19,"is_corresponding":false},{"id":1599,"name":"Manja  Jargosch","orcid":"0000-0001-6051-4036","position":20,"is_corresponding":false},{"id":1598,"name":"Ali Farnoud","orcid":"0000-0002-9298-5497","position":21,"is_corresponding":false},{"id":1600,"name":"Emanuele Scala","orcid":"0000-0001-6848-3262","position":22,"is_corresponding":false},{"id":1601,"name":"Anna Caroline Pilz","orcid":"0000-0002-3028-4556","position":23,"is_corresponding":false},{"id":1246,"name":"Jenny Thomas","orcid":"0000-0002-6386-7352","position":24,"is_corresponding":false},{"id":1604,"name":"Mona Ståhle","orcid":"0000-0002-3916-9343","position":25,"is_corresponding":false},{"id":1250,"name":"Natalie Garzorz-Stark","orcid":"0000-0002-7409-7883","position":26,"is_corresponding":false},{"id":1255,"name":"Kilian Eyerich","orcid":"0000-0003-0094-2674","position":27,"is_corresponding":false},{"id":1596,"name":"Alexander Schäbitz","orcid":"0000-0003-0945-7683","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":"36513651","pmcid":"PMC9747967","fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":"gold","license":"cc-by","views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":65.0,"fair_a":67.5,"fair_i":25.0,"fair_r":41.6667,"fair_zscore":0.4143,"fair_rationale":{"fair_score":49.79,"has_llm":true,"dimensions":{"F":{"name":"Findable","score":65.0,"criteria":[{"key":"f_has_doi","label":"Has a persistent DOI","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"DOI present","rationale":null},{"key":"f_repository_presence","label":"Indexed in repositories / literature DBs","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"datacite=0, pmcid=True, pmid=True","rationale":null},{"key":"f_persistent_ids","label":"Resolvable scholarly identifiers (OpenAlex)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no OpenAlex id","rationale":null},{"key":"f_metadata_richness","label":"Rich, machine-readable metadata","kind":"llm","weight":1.0,"fraction":0.5,"signal":null,"rationale":"The paper provides a data availability statement and GEO accession number (GSE206391), but does not describe structured, machine-readable metadata beyond the basic GEO record."}]},"A":{"name":"Accessible","score":67.5,"criteria":[{"key":"a_open_access","label":"Open Access / files deposited","kind":"deterministic","weight":1.5,"fraction":1.0,"signal":"Open Access","rationale":null},{"key":"a_retrievable","label":"Free full text retrievable","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"0 OA location(s)","rationale":null},{"key":"a_access_protocol","label":"Clear data/code access protocol","kind":"llm","weight":1.0,"fraction":0.75,"signal":null,"rationale":"The data access protocol is clearly stated via GEO, and code is available on GitHub and Zenodo, but no DOI is provided for the code and no explicit permanent identifier for the code is given."}]},"I":{"name":"Interoperable","score":25.0,"criteria":[{"key":"i_linked_data","label":"Linked datasets / DataCite relations","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"linked_datasets=0, datacite=0","rationale":null},{"key":"i_standard_ids","label":"References data via standard accessions","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"accessions=0, trials=0","rationale":null},{"key":"i_standards","label":"Standard formats, vocabularies & identifiers","kind":"llm","weight":1.0,"fraction":0.5,"signal":null,"rationale":"The study uses standard formats (FASTQ, UMI counts) and standard vocabularies (HGNC gene symbols, GO), but does not reference any formal ontology or semantic framework for interoperability."}]},"R":{"name":"Reusable","score":41.67,"criteria":[{"key":"r_license","label":"Clear, open reuse license","kind":"deterministic","weight":1.5,"fraction":0.0,"signal":"no license","rationale":null},{"key":"r_downloads","label":"Demonstrated reuse (downloads)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"downloads=0","rationale":null},{"key":"r_version","label":"Versioned / maintained","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no version chain","rationale":null},{"key":"r_dataset","label":"Classified as a data resource","kind":"deterministic","weight":0.5,"fraction":1.0,"signal":"is_dataset","rationale":null},{"key":"r_reusability","label":"Data-availability statement, license & reproducibility","kind":"llm","weight":2.0,"fraction":0.667,"signal":null,"rationale":"The paper includes a CC-BY 4.0 license, data and code availability statements, and detailed methods, but lacks a formal data usage license beyond the CC-BY and does not provide a structured metadata file for automated reuse."}]}},"suggestions":["Include a formal, machine-readable metadata file (e.g., ISA-Tab or JSON-LD) describing samples, protocols, and variables.","Provide a persistent identifier (e.g., DOI) for the code repository and ensure all code dependencies are clearly versioned.","Use standard ontologies (e.g., OBI, EFO) for experimental variables and tissue annotations to enhance interoperability.","Include a formal data usage license (e.g., CC0 or ODC-BY) for the dataset in addition to the article's CC-BY license.","Add a structured README file that describes file naming conventions, column headers, and units for all supplementary data files."],"model":"deepseek/deepseek-v4-flash","agent_version":"fair_agent_v2","fulltext_source":"epmc_xml"},"fair_model":"deepseek/deepseek-v4-flash","fair_agent_version":"fair_agent_v2","fair_fulltext_source":"epmc_xml","fair_has_llm":true,"fair_computed_at":"2026-06-18T00:40:57.146029Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}