{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T01:50:13Z","timestamp":1783561813306,"version":"3.55.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T00:00:00Z","timestamp":1645574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The limbus is located at a 2-mm-wide area between the bulbar conjunctiva and the cornea and has been suggested to be the niche of corneal epithelial stem cells and immune cells. Like the skin and intestines, the cornea is also an important mucosal surface, and immune cells on the cornea play critical roles in immune surveillance to ensure barrier surface homeostasis and protection from various environmental damage and infections. Single-cell RNA sequencing (scRNA-seq) analysis of protein tyrosine phosphatase receptor type C positive (PTPRC<jats:sup>+<\/jats:sup>) hematopoietic cells from the corneal limbus could provide a single cell atlas of all the immune cell subsets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed single-cell RNA sequencing to generate transcriptomic profile for 804 sort-purified hematopoietic cells from the corneal limbus of three healthy donors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our analysis identified a primary transcriptomic pattern for multiple immune cell subtypes, including naive T cells, antiviral effector CD8<jats:sup>+<\/jats:sup> T cells, and innate immune cells such as IDO1<jats:sup>+<\/jats:sup> mature regulatory dendritic cells (mregDCs), macrophages, monocytes, and basophils in the human corneal limbus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Overall, single-cell transcriptomic analysis of limbal immune cells suggested the possible contribution of these cells on the adaptive and innate immune response of the human cornea.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.798346","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T15:13:24Z","timestamp":1645629204000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Molecular Characteristics and Distribution of Adult Human Corneal Immune Cell Types"],"prefix":"10.3389","volume":"13","author":[{"given":"Yanxiu","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weitao","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1097\/APO.0b013e31828372c2","article-title":"Burden of Ocular Surface Disease in Patients With Glaucoma From Australia","volume":"2","author":"Chan","year":"2013","journal-title":"Asia Pac J Ophthalmol (Phila)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcrs.2010.12.037","article-title":"Anatomy and Physiology of the Cornea","volume":"37","author":"DelMonte","year":"2011","journal-title":"J Cataract Refract Surg"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/sj.eye.6700617","article-title":"Immune Defense at the Ocular Surface","volume":"17","author":"Akpek","year":"2003","journal-title":"Eye (Lond)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0000000000000088","article-title":"T Helper Subsets in Allergic Eye Disease","volume":"14","author":"Reyes","year":"2014","journal-title":"Curr Opin Allergy Clin Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2019.0060","article-title":"The Immunological Basis of Dry Eye Disease and Current Topical Treatment Options","volume":"36","author":"Periman","year":"2020","journal-title":"J Ocul Pharmacol Ther"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/srep45312","article-title":"Tissue Resident Memory T Cells in the Human Conjunctiva and Immune Signatures in Human Dry Eye Disease","volume":"7","author":"Bose","year":"2017","journal-title":"Sci Rep"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2532314","article-title":"Innate and Adaptive Cell Populations Driving Inflammation in Dry Eye Disease","volume":"2018","author":"Reyes","year":"2018","journal-title":"Mediators Inflamm"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1012524","article-title":"Dendritic Cell-Derived Thrombospondin-1 Is Critical for the Generation of the Ocular Surface Th17 Response to Desiccating Stress","volume":"94","author":"Gandhi","year":"2013","journal-title":"J Leukoc Biol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.immuni.2017.06.014","article-title":"An Ocular Commensal Protects Against Corneal Infection by Driving an Interleukin-17 Response From Mucosal Gammadelta T Cells","volume":"47","author":"St Leger","year":"2017","journal-title":"Immunity"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2110","DOI":"10.3390\/jcm8122110","article-title":"The Innate Immune Cell Profile of the Cornea Predicts the Onset of Ocular Surface Inflammatory Disorders","author":"Palomar","year":"2019","journal-title":"J Clin Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2010.26","article-title":"Autoimmunity at the Ocular Surface: Pathogenesis and Regulation","volume":"3","author":"Stern","year":"2010","journal-title":"Mucosal Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.620284","article-title":"Resident Innate Immune Cells in the Cornea","volume":"12","author":"Liu","year":"2021","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.135121","article-title":"Organogenesis and Distribution of the Ocular Lymphatic Vessels in the Anterior Eye","volume":"5","author":"Wu","year":"2020","journal-title":"JCI Insight"},{"key":"B14","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/978-1-0716-0599-8_3","article-title":"Primary Culture of Cornea-Limbal Epithelial Cells In Vitro","volume":"2145","author":"O'Sullivan","year":"2020","journal-title":"Methods Mol Biol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.cell.2016.12.022","article-title":"Systemic Immunity Is Required for Effective Cancer Immunotherapy","volume":"168","author":"Spitzer","year":"2017","journal-title":"Cell"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.047","article-title":"Data-Driven Phenotypic Dissection of AML Reveals Progenitor-Like Cells That Correlate With Prognosis","volume":"162","author":"Levine","year":"2015","journal-title":"Cell"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape Provides a Biologist-Oriented Resource for the Analysis of Systems-Level Datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat Commun"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1172\/JCI22325","article-title":"Regulatory T Cells can Migrate to Follicles Upon T Cell Activation and Suppress GC-Th Cells and GC-Th Cell-Driven B Cell Responses","volume":"114","author":"Lim","year":"2004","journal-title":"J Clin Invest"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2021.03.010","article-title":"A Single Cell Atlas of Human Cornea That Defines Its Development, Limbal Progenitor Cells and Their Interactions With the Immune Cells","volume":"21","author":"Collin","year":"2021","journal-title":"Ocul Surf"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.2174\/1389202921999200716103758","article-title":"Discrepant mRNA and Protein Expression in Immune Cells","volume":"21","author":"Li","year":"2020","journal-title":"Curr Genomics"},{"key":"B21","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1002\/eji.201948405","article-title":"CD96 Functions as a Co-Stimulatory Receptor to Enhance CD8(+) T Cell Activation and Effector Responses","volume":"50","author":"Chiang","year":"2020","journal-title":"Eur J Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2834","article-title":"The Transcription Factor BATF Operates as an Essential Differentiation Checkpoint in Early Effector CD8+ T Cells","volume":"15","author":"Kurachi","year":"2014","journal-title":"Nat Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.371","article-title":"CXCL16 and CXCR6 Are Upregulated in Psoriasis and Mediate Cutaneous Recruitment of Human CD8+ T Cells","volume":"132","author":"Gunther","year":"2012","journal-title":"J Invest Dermatol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20202345","article-title":"Single-Cell Analysis of Human Skin Identifies CD14+ Type 3 Dendritic Cells Co-Producing IL1B and IL23A in Psoriasis","volume":"218","author":"Nakamizo","year":"2021","journal-title":"J Exp Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2021.04.010","article-title":"Molecular Identity of Human Limbal Heterogeneity Involved in Corneal Homeostasis and Privilege","volume":"21","author":"Dou","year":"2021","journal-title":"Ocul Surf"},{"key":"B26","doi-asserted-by":"publisher","first-page":"16323","DOI":"10.1038\/s41598-021-94933-8","article-title":"Molecular Characteristics and Spatial Distribution of Adult Human Corneal Cell Subtypes","volume":"11","author":"Ligocki","year":"2021","journal-title":"Sci Rep"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nri3433","article-title":"The Ageing Haematopoietic Stem Cell Compartment","volume":"13","author":"Geiger","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2020.101231","article-title":"Thymus Involution Sets the Clock of the Aging T-Cell Landscape: Implications for Declined Immunity and Tissue Repair","volume":"65","author":"Elyahu","year":"2021","journal-title":"Ageing Res Rev"},{"key":"B29","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1038\/s41590-021-00965-7","article-title":"BATF Regulates Progenitor to Cytolytic Effector CD8(+) T Cell Transition During Chronic Viral Infection","volume":"22","author":"Chen","year":"2021","journal-title":"Nat Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200208)32:8<2255::AID-IMMU2255>3.0.CO;2-A","article-title":"Phenotypic Analysis of the Murine CD4-Related Glycoprotein, CD223 (LAG-3)","volume":"32","author":"Workman","year":"2002","journal-title":"Eur J Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200940234","article-title":"Loss of DNAM-1 Contributes to CD8+ T-Cell Exhaustion in Chronic HIV-1 Infection","volume":"40","author":"Cella","year":"2010","journal-title":"Eur J Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1200063","article-title":"CD8+ T Cells Suppress Viral Replication in the Cornea But Contribute to VEGF-C-Induced Lymphatic Vessel Genesis","volume":"189","author":"Conrady","year":"2012","journal-title":"J Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2020.11.002","article-title":"Prevalence of SARS-CoV-2 in Human Post-Mortem Ocular Tissues","volume":"19","author":"Sawant","year":"2021","journal-title":"Ocul Surf"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2020.6339","article-title":"Presence of SARS-CoV-2 RNA in the Cornea of Viremic Patients With COVID-19","volume":"139","author":"Casagrande","year":"2021","journal-title":"JAMA Ophthalmol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0782-6","article-title":"Broad and Strong Memory CD4(+) and CD8(+) T Cells Induced by SARS-CoV-2 in UK Convalescent Individuals Following COVID-19","volume":"21","author":"Peng","year":"2020","journal-title":"Nat Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21306","article-title":"Expression and Regulation of the Chemokine CXCL16 in Crohn's Disease and Models of Intestinal Inflammation","volume":"16","author":"Diegelmann","year":"2010","journal-title":"Inflamm Bowel Dis"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190811","article-title":"Re-Evaluation of Human BDCA-2+ DC During Acute Sterile Skin Inflammation","volume":"217","author":"Chen","year":"2020","journal-title":"J Exp Med"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.01.042","article-title":"Single-Cell Transcriptome Analysis of Human Skin Identifies Novel Fibroblast Subpopulation and Enrichment of Immune Subsets in Atopic Dermatitis","volume":"145","author":"He","year":"2020","journal-title":"J Allergy Clin Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/nri1457","article-title":"IDO Expression by Dendritic Cells: Tolerance and Tryptophan Catabolism","volume":"4","author":"Mellor","year":"2004","journal-title":"Nat Rev Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.798346\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T15:13:31Z","timestamp":1645629211000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.798346\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,23]]},"references-count":39,"alternative-id":["10.3389\/fimmu.2022.798346"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.798346","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,23]]},"article-number":"798346"}}