{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T22:43:38Z","timestamp":1789425818171,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T00:00:00Z","timestamp":1654473600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T00:00:00Z","timestamp":1654473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH1810628"],"award-info":[{"award-number":["W81XWH1810628"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recessive dystrophic epidermolysis bullosa (RDEB) patients develop poorly healing skin wounds that are frequently colonized with microbiota. Because T cells play an important role in clearing such pathogens, we aimed to define the status of adaptive T cell\u2010mediated immunity in RDEB wounds. Using a non\u2010invasive approach for sampling of wound\u2010associated constituents, we evaluated microbial contaminants in cellular fraction and exudates obtained from RDED wounds. Infectivity and intracellular trafficking of inactivated <jats:italic>Staphylococcus aureus<\/jats:italic> was accessed in RDEB keratinocytes. <jats:italic>S. aureus<\/jats:italic> and microbial antigen\u2010specific activation of RDEB wound\u2010derived T cells were investigated by fluorescence\u2010activated cell sorting\u2010based immune\u2010phenotyping and T\u2010cell functional assays. We found that RDEB wounds and epithelial cells are most frequently infected with <jats:italic>Staphylococcus<\/jats:italic> sp. and <jats:italic>Pseudomonas<\/jats:italic> sp. and that <jats:italic>S. aureus<\/jats:italic> essentially infects more RDEB keratinocytes and RDEB\u2010derived squamous cell carcinoma cells than keratinocytes from healthy donors. The RDEB wound\u2010associated T cells contain populations of CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> peripheral memory T cells that respond to soluble microbial antigens by proliferating and secreting interferon gamma (IFN\u03b3). Moreover, CD8<jats:sup>+<\/jats:sup> cytotoxic T lymphocytes recognize <jats:italic>S. aureus<\/jats:italic>\u2010infected RDEB keratinocytes and respond by producing interleukin\u20102 (IL\u20102) and IFN\u03b3 and degranulating and cytotoxically killing infected cells. Prolonged exposure of RDEB\u2010derived T cells to microbial antigens in vitro does not trigger PD\u20101\u2010mediated T\u2010cell exhaustion but induces differentiation of the CD4<jats:sup>high<\/jats:sup> population into CD4<jats:sup>high<\/jats:sup>CD25<jats:sup>+<\/jats:sup>FoxP3<jats:sup>+<\/jats:sup> regulatory T cells. Our data demonstrated that adaptive T cell\u2010mediated immunity could clear infected cells from wound sites, but these effects might be inhibited by PD\u20101\/Treg\u2010mediated immuno\u2010suppression in RDEB.<\/jats:p>","DOI":"10.1111\/exd.14615","type":"journal-article","created":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T07:38:48Z","timestamp":1653637128000},"page":"1431-1442","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["T\u2010cell activation and bacterial infection in skin wounds of recessive dystrophic epidermolysis bullosa patients"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0762-1833","authenticated-orcid":false,"given":"Vitali","family":"Alexeev","sequence":"first","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2947-021X","authenticated-orcid":false,"given":"Leonie","family":"Huitema","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9843-4736","authenticated-orcid":false,"given":"Taylor","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1106-8989","authenticated-orcid":false,"given":"Rodrigo","family":"Cepeda","sequence":"additional","affiliation":[{"name":"DEBRA MEXICO  Guadalupe Mexico"},{"name":"Julio Salas Dermatology  Guadalupe Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6576-6195","authenticated-orcid":false,"given":"Diego","family":"de los Cobos","sequence":"additional","affiliation":[{"name":"DEBRA MEXICO  Guadalupe Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9626-8682","authenticated-orcid":false,"given":"Regina Isabella Matus","family":"Perez","sequence":"additional","affiliation":[{"name":"DEBRA MEXICO  Guadalupe Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2076-2312","authenticated-orcid":false,"given":"Mauricio","family":"Salas\u2010Garza","sequence":"additional","affiliation":[{"name":"DEBRA MEXICO  Guadalupe Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7893-8379","authenticated-orcid":false,"given":"Oscar R.","family":"Fajardo\u2010Ramirez","sequence":"additional","affiliation":[{"name":"School of Medicine and Health Sciences Thechnological University of Monterrey  Monterrey Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4812-4734","authenticated-orcid":false,"given":"Franziska","family":"Ringpfeil","sequence":"additional","affiliation":[{"name":"Ringpfeil Advanced Dermatology  Haverford Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4639-807X","authenticated-orcid":false,"given":"Jouni","family":"Uitto","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7307-3898","authenticated-orcid":false,"given":"Julio Cesar","family":"Salas\u2010Alanis","sequence":"additional","affiliation":[{"name":"DEBRA MEXICO  Guadalupe Mexico"},{"name":"Julio Salas Dermatology  Guadalupe Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9813-7184","authenticated-orcid":false,"given":"Olga","family":"Igoucheva","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2018.04.001"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.12788\/j.sder.0087"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.det.2010.01.004"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.14235"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2020.10.009"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1470.2009.01070.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.02242"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M609784200"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.05642-11"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00104-12"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.581713"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3862"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201100173"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1709111115"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2017.07.002"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3307"},{"key":"e_1_2_9_18_1","first-page":"467","article-title":"Neutrophil\u2010mediated phagocytosis of Staphylococcus aureus","volume":"5","author":"Kessel KP","year":"2014","journal-title":"Front Immunol"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2008.02863.x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2006.05.007"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep23089"},{"issue":"3","key":"e_1_2_9_22_1","article-title":"Strategies used by bacteria to grow in macrophages","volume":"4","author":"Mitchell G","year":"2016","journal-title":"Microbiol Spectr"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3160"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0952-7915(91)90004-K"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-08-0905"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12030541"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01432-18"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2021.159057"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1402637111"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2012.00052"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20132577"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401936"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.3MR0120-390R"},{"issue":"6","key":"e_1_2_9_34_1","first-page":"2522","article-title":"CCL11 increases the proportion of CD4+CD25+Foxp3+ Treg cells and the production of IL2 and TGFbeta by CD4+ T cells via the STAT5 signaling pathway","volume":"21","author":"Wang R","year":"2020","journal-title":"Mol Med Rep"}],"container-title":["Experimental Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/exd.14615","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/exd.14615","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/exd.14615","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/exd.14615","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T08:58:07Z","timestamp":1692694687000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/exd.14615"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,6]]},"references-count":33,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2022,9]]}},"alternative-id":["10.1111\/exd.14615"],"URL":"https:\/\/doi.org\/10.1111\/exd.14615","archive":["Portico"],"relation":{},"ISSN":["0906-6705","1600-0625"],"issn-type":[{"value":"0906-6705","type":"print"},{"value":"1600-0625","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,6]]},"assertion":[{"value":"2021-11-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}