{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:39:07Z","timestamp":1790509147256,"version":"4.1.0"},"reference-count":27,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T00:00:00Z","timestamp":1601424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001787","name":"University of South Australia","doi-asserted-by":"publisher","award":["New Adventure Fund Grant"],"award-info":[{"award-number":["New Adventure Fund Grant"]}],"id":[{"id":"10.13039\/501100001787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009727","name":"The Hospital Research Foundation","doi-asserted-by":"publisher","award":["Project funding"],"award-info":[{"award-number":["Project funding"]}],"id":[{"id":"10.13039\/100009727","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Psoriasis is a common chronic inflammatory skin condition manifested by T cell responses and characterized by preferential recurrence at previously inflamed sites upon withdrawal of treatment. The site-specific disease memory in psoriasis has been linked to CD8+CD103+ tissue-resident memory T cells (Trm) in the epidermis which were previously thought to only provide \u201cfrontline\u201d protection against pathogens and immunosurveillance during cancer development. In this study, we correlated the presence of a subset of the Trm cells which are also CD49a+ with disease severity in human psoriatic lesions with acute and chronic disease. Using an imiquimod (IMQ)-induced murine model of psoriasiform dermatitis, we also investigated the level of CD49a+ Trm cells in acute, chronic and resolved psoriatic lesions. Investigation of clinical human samples showed that patient disease severity highly correlated with the numbers of epidermal CD49a+ Trm cells. Additionally, this subset of Trm cells was shown to persist in resolved lesions of murine psoriasiform dermatitis once clinical disease features had subsided. Importantly, these CD49a+ Trm cells showed significantly higher levels of granzyme B (GzmB) production compared to acute disease, suggesting a potential role of CD49a+ Trm cells for psoriatic re-occurrence in resolved patients. Better understanding of epidermal CD49a+ Trm cell activity is necessary for development of advanced treatment strategies for psoriasis to permit long-term, continuous disease control.<\/jats:p>","DOI":"10.3390\/ijms21197228","type":"journal-article","created":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T09:41:01Z","timestamp":1601458861000},"page":"7228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Immunological Memory in Imiquimod-Induced Murine Model of Psoriasiform Dermatitis"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1619-1406","authenticated-orcid":false,"given":"Kevin","family":"Fenix","sequence":"first","affiliation":[{"name":"Basil Hetzel Institute for Translational Health Research, Discipline of Surgery, Adelaide Medical School, The University of Adelaide, Woodville South, Adelaide, SA 5011, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danushka K.","family":"Wijesundara","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane City, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2885-2080","authenticated-orcid":false,"given":"Allison J.","family":"Cowin","sequence":"additional","affiliation":[{"name":"Future Industries Institute, University of South Australia, Mawson Lakes, Adelaide, SA 5095, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4642-105X","authenticated-orcid":false,"given":"Branka","family":"Grubor-Bauk","sequence":"additional","affiliation":[{"name":"Basil Hetzel Institute for Translational Health Research, Discipline of Surgery, Adelaide Medical School, The University of Adelaide, Woodville South, Adelaide, SA 5011, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8072-4222","authenticated-orcid":false,"given":"Zlatko","family":"Kopecki","sequence":"additional","affiliation":[{"name":"Future Industries Institute, University of South Australia, Mawson Lakes, Adelaide, SA 5095, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Radi, G., Campanati, A., Diotallevi, F., Bianchelli, T., and Offidani, A. (2020). Novel Therapeutic Approaches and Targets for Treatment of Psoriasis. Curr. Pharm. Biotechnol.","DOI":"10.2174\/1389201021666200629150231"},{"key":"ref_2","first-page":"97","article-title":"Current Developments in the Immunology of Psoriasis","volume":"93","author":"Gran","year":"2020","journal-title":"Yale J. Biol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"168321","DOI":"10.1155\/2013\/168321","article-title":"Lifting the silver flakes: The pathogenesis and management of chronic plaque psoriasis","volume":"2013","author":"Chong","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.jaci.2017.07.004","article-title":"Psoriasis pathogenesis and the development of novel targeted immune therapies","volume":"140","author":"Hawkes","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Owczarczyk Saczonek, A., Krajewska-Wlodarczyk, M., Kasprowicz-Furmanczyk, M., and Placek, W. (2020). Immunological Memory of Psoriatic Lesions. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020625"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Rendon, A., and Schakel, K. (2019). Psoriasis Pathogenesis and Treatment. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061475"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1007\/s00281-019-00766-z","article-title":"Resolution of plaque-type psoriasis: What is left behind (and reinitiates the disease)","volume":"41","author":"Benezeder","year":"2019","journal-title":"Semin. Immunopathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3111","DOI":"10.4049\/jimmunol.1302313","article-title":"Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis","volume":"192","author":"Cheuk","year":"2014","journal-title":"J. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.immuni.2017.01.009","article-title":"CD49a Expression Defines Tissue-Resident CD8+ T Cells Poised for Cytotoxic Function in Human Skin","volume":"46","author":"Cheuk","year":"2017","journal-title":"Immunity"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"12306","DOI":"10.1073\/pnas.1915681117","article-title":"TRM integrins CD103 and CD49a differentially support adherence and motility after resolution of influenza virus infection","volume":"117","author":"Reilly","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"515","DOI":"10.3389\/fimmu.2018.00515","article-title":"Tissue-Resident Memory CD8+ T Cells: From Phenotype to Function","volume":"9","author":"Topham","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1172\/JCI7911","article-title":"Regulation of inflammation by collagen-binding integrins alpha1beta1 and alpha2beta1 in models of hypersensitivity and arthritis","volume":"105","author":"Sprague","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1016\/j.bbagen.2013.12.022","article-title":"Molecular composition and function of integrin-based collagen glues-introducing COLINBRIs","volume":"1840","author":"Zeltz","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1038\/nm1605","article-title":"Alpha1beta1 integrin is crucial for accumulation of epidermal T cells and the development of psoriasis","volume":"13","author":"Conrad","year":"2007","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/nature05652","article-title":"Semaphorin 7A initiates T-cell-mediated inflammatory responses through alpha1beta1 integrin","volume":"446","author":"Suzuki","year":"2007","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1038\/ni.2744","article-title":"The developmental pathway for CD103+CD8+ tissue-resident memory T cells of skin","volume":"14","author":"Mackay","year":"2013","journal-title":"Nat. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1016\/j.jaci.2018.08.048","article-title":"A skewed pool of resident T cells triggers psoriasis-associated tissue responses in never-lesional skin from patients with psoriasis","volume":"143","author":"Hoffer","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/s41423-019-0359-1","article-title":"Local heroes or villains: Tissue-resident memory T cells in human health and disease","volume":"17","author":"Sasson","year":"2020","journal-title":"Cell. Mol. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5836","DOI":"10.4049\/jimmunol.0802999","article-title":"Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23\/IL-17 axis","volume":"182","author":"Mourits","year":"2009","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1111\/bjd.14842","article-title":"Reducing Flightless I expression decreases severity of psoriasis in an imiquimod-induced murine model of psoriasiform dermatitis","volume":"176","author":"Chong","year":"2017","journal-title":"Br. J. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/jid.2010.280","article-title":"Resolved psoriasis lesions retain expression of a subset of disease-related genes","volume":"131","author":"Lowes","year":"2011","journal-title":"J. Invesig. Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4031","DOI":"10.1172\/JCI93396","article-title":"Clinically resolved psoriatic lesions contain psoriasis-specific IL-17-producing alphabeta T cell clones","volume":"127","author":"Matos","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1016\/j.jid.2018.02.030","article-title":"Cells in Resolved Psoriasis Steer Tissue Responses that Stratify Clinical Outcome","volume":"138","author":"Classon","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1111\/bjd.17748","article-title":"CD8 resident memory T cells with interleukin 17A-producing potential are accumulated in disease-naive nonlesional sites of psoriasis possibly in correlation with disease duration","volume":"181","author":"Vo","year":"2019","journal-title":"Br. J. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1046\/j.1365-2133.2001.04222.x","article-title":"Perforin and granzyme B may contribute to skin inflammation in atopic dermatitis and psoriasis","volume":"144","author":"Yawalkar","year":"2001","journal-title":"Br. J. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.jid.2016.11.033","article-title":"Dynamic Changes in Resident and Infiltrating Epidermal Dendritic Cells in Active and Resolved Psoriasis","volume":"137","author":"Martini","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.3389\/fimmu.2018.01833","article-title":"Flightless I Alters the Inflammatory Response and Autoantibody Profile in an OVA-Induced Atopic Dermatitis Skin-Like Disease","volume":"9","author":"Kopecki","year":"2018","journal-title":"Front. Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/19\/7228\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:15:15Z","timestamp":1760177715000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/19\/7228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,30]]},"references-count":27,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["ijms21197228"],"URL":"https:\/\/doi.org\/10.3390\/ijms21197228","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,30]]}}}