{"doi":"10.1172/jci.insight.187381","title":"Resident memory T cell development is gradual and shows AP-1 gene expression in mature cells","abstract":"<jats:p>\n                    Tissue-resident memory T (T\n                    <jats:sub>RM</jats:sub>\n                    ) cells play a central role in immune responses across all barrier tissues after infection. However, the mechanisms that drive T\n                    <jats:sub>RM</jats:sub>\n                    differentiation and priming for their recall effector function remains unclear. In this study, we leveraged newly generated and publicly available single-cell RNA-seq data generated across 10 developmental time points to define features of CD8\n                    <jats:sup>+</jats:sup>\n                    T\n                    <jats:sub>RM</jats:sub>\n                    across both skin and small-intestine intraepithelial lymphocytes (siIEL). We employed linear modeling to capture gene programs that increase their expression levels in T cells transitioning from an effector to a memory state. In addition to capturing tissue-specific gene programs, we defined a temporal T\n                    <jats:sub>RM</jats:sub>\n                    signature across skin and siIEL that can distinguish T\n                    <jats:sub>RM</jats:sub>\n                    from circulating T cell populations. This T\n                    <jats:sub>RM</jats:sub>\n                    signature highlights biology that is missed in published signatures that compared bulk T\n                    <jats:sub>RM</jats:sub>\n                    to naive or nontissue resident memory populations. This temporal T\n                    <jats:sub>RM</jats:sub>\n                    signature included the AP-1 transcription factor family members\n                    <jats:italic>Fos, Fosb,</jats:italic>\n                    <jats:italic>Fosl2</jats:italic>\n                    , and\n                    <jats:italic>Junb</jats:italic>\n                    . ATAC-seq analysis detected AP-1–specific motifs at open chromatin sites in mature T\n                    <jats:sub>RM</jats:sub>\n                    . Cyclic immunofluorescence (CyCIF) tissue imaging detected nuclear colocalization of AP-1 members in resting CD8\n                    <jats:sup>+</jats:sup>\n                    T\n                    <jats:sub>RM</jats:sub>\n                    greater than 100 days after infection. Taken together, these results reveal a critical role of AP-1 transcription factor members in T\n                    <jats:sub>RM</jats:sub>\n                    biology.\n                  </jats:p>","journal":"JCI Insight","year":2025,"id":630283,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1132541,"name":"Yu Yan","orcid":"0000-0003-2630-0178","position":1,"is_corresponding":false},{"id":503740,"name":"Youdong Pan","orcid":null,"position":2,"is_corresponding":false},{"id":489799,"name":"Jason B. Williams","orcid":"0000-0002-8386-6285","position":3,"is_corresponding":false},{"id":89071,"name":"Kasidet Manakongtreecheep","orcid":"0000-0002-4182-9603","position":4,"is_corresponding":false},{"id":1232598,"name":"Shishir M. Pant","orcid":"0000-0002-2686-7898","position":5,"is_corresponding":false},{"id":502586,"name":"Jingxia Zhao","orcid":"0009-0003-4553-7274","position":6,"is_corresponding":false},{"id":963158,"name":"Tian Tian","orcid":"0000-0002-0224-2957","position":7,"is_corresponding":false},{"id":1021375,"name":"Timothy Pan","orcid":"0009-0006-4328-1174","position":8,"is_corresponding":false},{"id":1632698,"name":"Claire Stingley","orcid":null,"position":9,"is_corresponding":false},{"id":956710,"name":"Kevin Wu","orcid":"0000-0003-1751-0018","position":10,"is_corresponding":false},{"id":399673,"name":"Jiang Zhang","orcid":"0000-0001-5807-1686","position":11,"is_corresponding":false},{"id":1632699,"name":"Alexander L. Kley","orcid":null,"position":12,"is_corresponding":false},{"id":24147,"name":"Peter K. Sorger","orcid":"0000-0002-3364-1838","position":13,"is_corresponding":false},{"id":14837,"name":"Alexandra–Chloé Villani","orcid":"0000-0001-7461-0408","position":14,"is_corresponding":false},{"id":292500,"name":"Thomas S. Kupper","orcid":"0000-0002-4229-2916","position":15,"is_corresponding":false},{"id":89090,"name":"Neal P. Smith","orcid":"0000-0003-1394-3158","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Resident memory T cell development is gradual and shows AP-1 gene expression in mature cells","abstract":"<jats:p>\n                    Tissue-resident memory T (T\n                    <jats:sub>RM</jats:sub>\n                    ) cells play a central role in immune responses across all barrier tissues after infection. However, the mechanisms that drive T\n                    <jats:sub>RM</jats:sub>\n                    differentiation and priming for their recall effector function remains unclear. In this study, we leveraged newly generated and publicly available single-cell RNA-seq data generated across 10 developmental time points to define features of CD8\n                    <jats:sup>+</jats:sup>\n                    T\n                    <jats:sub>RM</jats:sub>\n                    across both skin and small-intestine intraepithelial lymphocytes (siIEL). We employed linear modeling to capture gene programs that increase their expression levels in T cells transitioning from an effector to a memory state. In addition to capturing tissue-specific gene programs, we defined a temporal T\n                    <jats:sub>RM</jats:sub>\n                    signature across skin and siIEL that can distinguish T\n                    <jats:sub>RM</jats:sub>\n                    from circulating T cell populations. This T\n                    <jats:sub>RM</jats:sub>\n                    signature highlights biology that is missed in published signatures that compared bulk T\n                    <jats:sub>RM</jats:sub>\n                    to naive or nontissue resident memory populations. This temporal T\n                    <jats:sub>RM</jats:sub>\n                    signature included the AP-1 transcription factor family members\n                    <jats:italic>Fos, Fosb,</jats:italic>\n                    <jats:italic>Fosl2</jats:italic>\n                    , and\n                    <jats:italic>Junb</jats:italic>\n                    . ATAC-seq analysis detected AP-1–specific motifs at open chromatin sites in mature T\n                    <jats:sub>RM</jats:sub>\n                    . Cyclic immunofluorescence (CyCIF) tissue imaging detected nuclear colocalization of AP-1 members in resting CD8\n                    <jats:sup>+</jats:sup>\n                    T\n                    <jats:sub>RM</jats:sub>\n                    greater than 100 days after infection. Taken together, these results reveal a critical role of AP-1 transcription factor members in T\n                    <jats:sub>RM</jats:sub>\n                    biology.\n                  </jats:p>","is_dataset_classified":null,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40548376","pmcid":"PMC12220954","openalex_id":"https://openalex.org/W4411523946","authors":[],"funders":[{"funder_name":"NIH Office of the Director","grant_id":"R01AR065807,R01AI127654,DP2CA247831,U2C-CA233262","title":null},{"funder_name":"NCI NIH HHS","grant_id":"DP2 CA247831","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI127654","title":null},{"funder_name":"NCI NIH HHS","grant_id":"U2C CA233262","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI175582","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"R01 AR065807","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01AI127654-02","title":"Generation of Robust Resident Memory T cells in Barrier Tissues through Skin Vaccination"},{"funder_name":"National Institutes of Health","grant_id":"1DP2CA247831-01","title":"Deciphering the Achilles Heel of Cancer Immunotherapy"},{"funder_name":"National Institutes of Health","grant_id":"5R01AR065807-23","title":"Skin Homing T Cells"},{"funder_name":"National Institutes of Health","grant_id":"1U2CCA233262-01","title":"Pre-cancer atlases of cutaneous and hematologic origin (PATCH Center)"}],"total_grants":10,"fwci":3.0939,"citation_percentile":0.92269141,"influential_citations":0,"citation_trend":[{"year":2025,"count":2},{"year":2026,"count":6}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1172/jci.insight.187381","host_type":"journal"},{"url":"https://doi.org/10.1172/jci.insight.187381","host_type":"publisher"},{"url":"https://insight.jci.org/articles/view/187381/files/pdf","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40548376","host_type":"repository"},{"url":"https://doaj.org/article/a7b7bb03753b406087d4f913bfbc2121","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12220954","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12220954","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12220954?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1172/jci.insight.187381","host_type":""}],"fields_of_study":["T-cell and B-cell Immunology","Immune Cell Function and Interaction","CAR-T cell therapy research","Transcription Factor AP-1","Animals","CD8-Positive T-Lymphocytes","Mice","Memory T Cells","Immunologic Memory","Proto-Oncogene Proteins c-fos","Cell Differentiation","Humans","Skin","Fos-Related Antigen-2","Single-Cell Analysis","Mice, Inbred C57BL","Transcription Factors"],"mesh_terms":["Memory T Cells","Animals","Cell Differentiation","Humans","Immunologic Memory","Mice, Inbred C57BL","Skin","Transcription Factors","Proto-Oncogene Proteins c-fos","CD8-Positive T-Lymphocytes","Transcription Factor AP-1","Mice","Fos-Related Antigen-2","Single-Cell Analysis"],"keywords":["Gene expression","Gene","Cell biology","Expression (computer science)","Cell","Biology","Cell growth","Memory development","Molecular biology","Chemistry","Genetics","Computer science","Neuroscience","Cognition","Inflammation","immunology","adaptive immunity","T Cell Development","Cell Differentiation","Fos-Related Antigen-2","CD8-Positive T-Lymphocytes","Transcription Factor AP-1","Mice, Inbred C57BL","Mice","Memory T Cells","Animals","Humans","Single-Cell Analysis","Immunologic Memory","Proto-Oncogene Proteins c-fos","Research Article","Skin","Transcription Factors"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"geo"},{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T20:50:12.984072Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}