{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:46:25Z","timestamp":1791895585300,"version":"4.3.4"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T00:00:00Z","timestamp":1616544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acne vulgaris and rosacea are common inflammatory complications of the skin, both characterized by abnormal infiltration of immune cells. The two diseases can be differentiated based on characteristic profile of the immune cell infiltrates at the periphery of disease lesions. In addition, dysregulated infiltration of immune cells not only occur in the acne lesions but also in non-lesional areas of patients with the disease, thus characterizing the immune infiltration in these sites can further enhance our understanding on the pathogenesis of acne.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Five microarray data-sets (GSE108110, GSE53795, GSE65914, GSE14905 and GSE78097) were downloaded from Gene Expression Omnibus. After removing the batch effects and normalizing the data, we applied the CIBERSORT algorithm combined with signature matrix LM22, to describe 22 types of immune cells\u2019 infiltration in acne less than 48 hour (H) old, in comparation with non-lesional skin of acne patients, healthy skin and rosacea (including erythematotelangiectatic rosacea, papulopustular rosacea and phymatous rosacea) and we compared gene expression of Th1 and Th17-related molecules in acne, rosacea and healthy control.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with the non-lesional skin of acne patients, healthy individuals and rosacea patients, there is a significant increase in infiltration of neutrophils, monocytes and activated mast cells around the acne lesions, less than 48 H after their development. Contrarily, few naive CD4+ T cells, plasma cells, memory B cells and resting mast cells infiltrate acne sites compared to the aforementioned groups of individuals. Moreover, the infiltration of Regulatory T cells (Tregs) in acne lesions is substantially lower, relative to non-lesional sites of acne patients and skin of healthy individuals. In addition, non-lesional sites of acne patients exhibit lower infiltration of activated memory CD4+ T cells, plasma cells, memory B cells, M0 macrophages, neutrophils, resting mast cells but higher infiltration of Tregs and resting dendritic cells relative to skin of healthy individuals. Intriguingly, we found that among the 3 rosacea subtypes, the immune infiltration profile of papulopustular rosacea is the closest to that of acne lesions. In addition, through gene expression analysis of acne, rosacea and skin tissues of healthy individuals, we found a higher infiltration of Th1 and Th17 cells in acne lesions, relative to non-lesional skin areas of acne patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study provides new insights into the inflammatory pathogenesis of acne, and the difference between acne and rosacea, which helps in differentiating the two diseases. Our findings also guide on appropriate target therapy of the immune cell infiltrates in the two disease conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0248650","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T13:43:42Z","timestamp":1616593422000},"page":"e0248650","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":38,"title":["Elucidating the immune infiltration in acne and its comparison with rosacea by integrated bioinformatics analysis"],"prefix":"10.1371","volume":"16","author":[{"given":"Lu","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Hong","family":"Shou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Sheng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Hua","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,3,24]]},"reference":[{"key":"pone.0248650.ref001","article-title":"Particularities of psychiatric and dermatological comorbidity among medical students in Morocco: Multicenter study","author":"M Barrimi","year":"2020","journal-title":"L\u2019Encephale"},{"issue":"18","key":"pone.0248650.ref002","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1056\/NEJMcp1506630","article-title":"Rosacea","volume":"377","author":"EJ van Zuuren","year":"2017","journal-title":"The New England journal of medicine"},{"issue":"2","key":"pone.0248650.ref003","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/jdv.14475","article-title":"Acne prevalence and associations with lifestyle: a cross-sectional online survey of adolescents\/young adults in 7 European countries","volume":"32","author":"P Wolkenstein","year":"2018","journal-title":"Journal of the European Academy of Dermatology and Venereology: JEADV"},{"issue":"9","key":"pone.0248650.ref004","first-page":"e5722","article-title":"Prevalence and Psychological Impact of Acne Vulgaris in Female Undergraduate Medical Students of Rawalpindi and Islamabad, Pakistan","volume":"11","author":"O Babar","year":"2019","journal-title":"Cureus"},{"issue":"6","key":"pone.0248650.ref005","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1016\/j.jaad.2013.04.043","article-title":"Rosacea: current state of epidemiology","volume":"69","author":"J Tan","year":"2013","journal-title":"Journal of the American Academy of Dermatology"},{"key":"pone.0248650.ref006","unstructured":"Sutaria AH, Masood S, Schlessinger J. Acne Vulgaris. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright \u00a9 2020, StatPearls Publishing LLC.; 2020."},{"issue":"5","key":"pone.0248650.ref007","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.jaad.2014.08.028","article-title":"Rosacea: part I. Introduction, categorization, histology, pathogenesis, and risk factors","volume":"72","author":"AM Two","year":"2015","journal-title":"Journal of the American Academy of Dermatology"},{"issue":"4","key":"pone.0248650.ref008","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1111\/bjd.16680","article-title":"Atrophic scar formation in patients with acne involves long-acting immune responses with plasma cells and alteration of sebaceous glands","volume":"179","author":"I Carlavan","year":"2018","journal-title":"The British journal of dermatology"},{"issue":"9","key":"pone.0248650.ref009","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1038\/jid.2015.141","article-title":"Molecular and Morphological Characterization of Inflammatory Infiltrate in Rosacea Reveals Activation of Th1\/Th17 Pathways","volume":"135","author":"T Buhl","year":"2015","journal-title":"The Journal of investigative dermatology"},{"issue":"8","key":"pone.0248650.ref010","doi-asserted-by":"crossref","first-page":"e105238","DOI":"10.1371\/journal.pone.0105238","article-title":"IL-17\/Th17 pathway is activated in acne lesions","volume":"9","author":"HL Kelh\u00e4l\u00e4","year":"2014","journal-title":"PloS one"},{"issue":"1","key":"pone.0248650.ref011","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s12920-019-0567-7","article-title":"Characterization of disease-specific cellular abundance profiles of chronic inflammatory skin conditions from deconvolution of biopsy samples","volume":"12","author":"ZC F\u00e9lix Garza","year":"2019","journal-title":"BMC medical genomics"},{"issue":"1","key":"pone.0248650.ref012","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s12865-019-0316-x","article-title":"Immune cell infiltration characteristics and related core genes in lupus nephritis: results from bioinformatic analysis","volume":"20","author":"Y Cao","year":"2019","journal-title":"BMC immunology"},{"key":"pone.0248650.ref013","doi-asserted-by":"crossref","first-page":"106246","DOI":"10.1016\/j.intimp.2020.106246","article-title":"Elucidating the molecular pathways and immune system transcriptome during ischemia-reperfusion injury in renal transplantation","volume":"81","author":"J Zhang","year":"2020","journal-title":"International immunopharmacology"},{"issue":"3","key":"pone.0248650.ref014","article-title":"GRB10 and E2F3 as Diagnostic Markers of Osteoarthritis and Their Correlation with Immune Infiltration","volume":"10","author":"YJ Deng","year":"2020","journal-title":"Diagnostics (Basel, Switzerland)"},{"key":"pone.0248650.ref015","doi-asserted-by":"crossref","first-page":"e8390","DOI":"10.7717\/peerj.8390","article-title":"Identification of key biomarkers and immune infiltration in the synovial tissue of osteoarthritis by bioinformatics analysis","volume":"8","author":"W Cai","year":"2020","journal-title":"PeerJ"},{"issue":"5","key":"pone.0248650.ref016","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nmeth.3337","article-title":"Robust enumeration of cell subsets from tissue expression profiles","volume":"12","author":"AM Newman","year":"2015","journal-title":"Nature methods"},{"issue":"3","key":"pone.0248650.ref017","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1093\/bioinformatics\/btg405","article-title":"affy\u2014analysis of Affymetrix GeneChip data at the probe level","volume":"20","author":"L Gautier","year":"2004","journal-title":"Bioinformatics (Oxford, England)"},{"issue":"19","key":"pone.0248650.ref018","doi-asserted-by":"crossref","first-page":"2757","DOI":"10.1093\/bioinformatics\/btu375","article-title":"Preserving biological heterogeneity with a permuted surrogate variable analysis for genomics batch correction","volume":"30","author":"HS Parker","year":"2014","journal-title":"Bioinformatics (Oxford, England)"},{"key":"pone.0248650.ref019","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s00357-005-0012-9","article-title":"Hierarchical Clustering via Joint Between-Within Distances: Extending Ward\u2019s Minimum Variance Method","volume":"22","author":"G Szekely","year":"2005","journal-title":"Journal of Classification"},{"issue":"2","key":"pone.0248650.ref020","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1209\/epl\/i2004-10483-y","article-title":"Hierarchical clustering using mutual information","volume":"70","author":"A Kraskov","year":"2005","journal-title":"Europhysics Letters (EPL)"},{"issue":"5","key":"pone.0248650.ref021","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.clinthera.2020.03.008","article-title":"Stress-induced Interaction of Skin Immune Cells, Hormones, and Neurotransmitters","volume":"42","author":"N Pondeljak","year":"2020","journal-title":"Clinical therapeutics"},{"key":"pone.0248650.ref022","first-page":"7","article-title":"Recent advances in understanding and managing rosacea","author":"J Buddenkotte","year":"2018","journal-title":"F1000Research"},{"issue":"4","key":"pone.0248650.ref023","doi-asserted-by":"crossref","first-page":"392","DOI":"10.4103\/ijd.IJD_483_16","article-title":"Propionibacterium acnes and the Th1\/Th17 Axis, Implications in Acne Pathogenesis and Treatment","volume":"62","author":"K Sardana","year":"2017","journal-title":"Indian journal of dermatology"},{"issue":"9813","key":"pone.0248650.ref024","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/S0140-6736(11)60321-8","article-title":"Acne vulgaris","volume":"379","author":"HC Williams","year":"2012","journal-title":"Lancet (London, England)"},{"issue":"4","key":"pone.0248650.ref025","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1067\/mjd.2002.120625","article-title":"Standard classification of rosacea: Report of the National Rosacea Society Expert Committee on the Classification and Staging of Rosacea","volume":"46","author":"J Wilkin","year":"2002","journal-title":"Journal of the American Academy of Dermatology"},{"issue":"6","key":"pone.0248650.ref026","first-page":"e175","article-title":"Rosacea: a wholistic review and update from pathogenesis to diagnosis and therapy","volume":"59","author":"JW Marson","journal-title":"International journal of dermatology"},{"issue":"5","key":"pone.0248650.ref027","doi-asserted-by":"crossref","first-page":"e13020","DOI":"10.1111\/dth.13020","article-title":"Acne and rosacea: What\u2019s new for treatment?","volume":"32","author":"R Dursun","year":"2019","journal-title":"Dermatologic therapy"},{"issue":"2","key":"pone.0248650.ref028","doi-asserted-by":"crossref","first-page":"87","DOI":"10.12788\/j.sder.2016.026","article-title":"Over-the-counter treatments for acne and rosacea","volume":"35","author":"LL Rosamilia","year":"2016","journal-title":"Seminars in cutaneous medicine and surgery"},{"issue":"12","key":"pone.0248650.ref029","doi-asserted-by":"crossref","DOI":"10.1016\/j.jid.2019.03.1161","article-title":"miR-146a Inhibits Biofilm-Derived Cutibacterium acnes-Induced Inflammatory Reactions in Human Keratinocytes","volume":"139","author":"R Zeng","year":"2019","journal-title":"The Journal of investigative dermatology"},{"issue":"3","key":"pone.0248650.ref030","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/jid.2013.438","article-title":"IL-1\u03b2 drives inflammatory responses to propionibacterium acnes in vitro and in vivo","volume":"134","author":"M Kistowska","year":"2014","journal-title":"The Journal of investigative dermatology"},{"issue":"1","key":"pone.0248650.ref031","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/jid.2014.290","article-title":"Propionibacterium acnes promotes Th17 and Th17\/Th1 responses in acne patients","volume":"135","author":"M Kistowska","year":"2015","journal-title":"The Journal of investigative dermatology"},{"issue":"3","key":"pone.0248650.ref032","doi-asserted-by":"crossref","first-page":"e13279","DOI":"10.1111\/dth.13279","article-title":"The potential of probiotics for treating acne vulgaris: A review of literature on acne and microbiota","volume":"33","author":"A Goodarzi","year":"2020","journal-title":"Dermatologic therapy"},{"issue":"5","key":"pone.0248650.ref033","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s00403-019-01908-x","article-title":"From pathogenesis of acne vulgaris to anti-acne agents","volume":"311","author":"TX Cong","year":"2019","journal-title":"Archives of dermatological research"},{"issue":"1","key":"pone.0248650.ref034","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1159\/000067818","article-title":"New aspects in acne inflammation","volume":"206","author":"M Toyoda","year":"2003","journal-title":"Dermatology (Basel, Switzerland)"},{"issue":"1","key":"pone.0248650.ref035","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41577-018-0084-5","article-title":"The immunological anatomy of the skin","volume":"19","author":"K Kabashima","year":"2019","journal-title":"Nature reviews Immunology"},{"issue":"5","key":"pone.0248650.ref036","doi-asserted-by":"crossref","first-page":"5920","DOI":"10.1021\/acsnano.9b01774","article-title":"The Skin You Are In: Design-of-Experiments Optimization of Lipid Nanoparticle Self-Amplifying RNA Formulations in Human Skin Explants","volume":"13","author":"AK Blakney","year":"2019","journal-title":"ACS nano"},{"issue":"7","key":"pone.0248650.ref037","doi-asserted-by":"crossref","first-page":"4431","DOI":"10.4049\/jimmunol.176.7.4431","article-title":"The vast majority of CLA+ T cells are resident in normal skin","volume":"176","author":"RA Clark","year":"2006","journal-title":"Journal of immunology (Baltimore, Md: 1950)"},{"issue":"279","key":"pone.0248650.ref038","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3010302","article-title":"Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells","volume":"7","author":"R Watanabe","year":"2015","journal-title":"Science translational medicine"},{"issue":"1","key":"pone.0248650.ref039","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1046\/j.1523-1747.2003.12321.x","article-title":"Inflammatory events are involved in acne lesion initiation","volume":"121","author":"AH Jeremy","year":"2003","journal-title":"The Journal of investigative dermatology"},{"issue":"11","key":"pone.0248650.ref040","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1046\/j.1365-4362.2001.01262.x","article-title":"Mast cell density and IL-8 expression in nonlesional and lesional psoriatic skin","volume":"40","author":"WY Jiang","year":"2001","journal-title":"International journal of dermatology"},{"key":"pone.0248650.ref041","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1146\/annurev-immunol-032712-095954","article-title":"Memory T cell subsets, migration patterns, and tissue residence","volume":"31","author":"SN Mueller","year":"2013","journal-title":"Annual review of immunology"},{"issue":"13","key":"pone.0248650.ref042","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1016\/j.yexcr.2009.04.013","article-title":"Adhesion and transcellular migration of neutrophils and B lymphocytes on fibroblasts","volume":"315","author":"P Couture","year":"2009","journal-title":"Experimental cell research"},{"issue":"5","key":"pone.0248650.ref043","doi-asserted-by":"crossref","first-page":"727","DOI":"10.3109\/08923973.2011.619987","article-title":"The deviated balance between regulatory T cell and Th17 in autoimmunity","volume":"34","author":"F Jadidi-Niaragh","year":"2012","journal-title":"Immunopharmacology and immunotoxicology"},{"issue":"1","key":"pone.0248650.ref044","doi-asserted-by":"crossref","DOI":"10.3390\/molecules22010134","article-title":"Therapeutic Potential of Targeting the Th17\/Treg Axis in Autoimmune Disorders","volume":"22","author":"P Fasching","year":"2017","journal-title":"Molecules (Basel, Switzerland)"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0248650","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T13:44:22Z","timestamp":1616593462000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0248650"}},"subtitle":[],"editor":[{"given":"Deyu","family":"Fang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,3,24]]},"references-count":44,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0248650","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,24]]}}}