{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T05:20:18Z","timestamp":1784956818732,"version":"3.55.0"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Funda\u00e7\u00e3o de Amparo a Pesquisa do Esp\u00edrito Santo","award":["2022-1TCGX and 2022-H5GWQ"],"award-info":[{"award-number":["2022-1TCGX and 2022-H5GWQ"]}]},{"name":"National Council for Scientific and Technological Development\u2014CNPq","award":["402280\/2022-9"],"award-info":[{"award-number":["402280\/2022-9"]}]},{"name":"Medical Research Council","award":["MR\/T015853\/1"],"award-info":[{"award-number":["MR\/T015853\/1"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-AI-149456"],"award-info":[{"award-number":["R01-AI-149456"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The American tegumentary leishmaniasis (ATL) is caused by protozoans of the genus Leishmania and varies from mild localized cutaneous leishmaniasis (LCL) form to more severe manifestations such as the diffuse cutaneous leishmaniasis (DCL) form and the mucosal leishmaniasis (ML) form. Previously, we demonstrated the accumulation of senescent cells in skin lesions of patients with LCL. Moreover, lesional transcriptomic analyses revealed a robust co-induction of senescence and pro-inflammatory gene signatures, highlighting the critical role of senescent T cells in orchestrating pathology. In this work we hypothesized that senescent cells might operate differently among the ATL spectrum, potentially influencing immunopathological mechanisms and clinical outcome. We analysed previously published RNA-Seq datasets of skin biopsies of healthy subjects and lesional skin from DCL patients, LCL patients, and LCL patients that, after treatment, progressed to mucosal leishmaniasis (MLP). Our findings demonstrate a robust presence of a CD8 T-cell signature associated with both LCL and MLP lesions. Moreover, both inflammatory and cytotoxic signatures were significantly upregulated, showing a strong increase in MLP and LCL groups, but not DCL. The senescence signature was elevated between LCL and MLP groups, representing the only distinguishable signature of immunopathology between them. Interestingly, our analyses further revealed the senescence signature\u2019s capacity to predict progression from LCL to mucosal forms, which was not observed with other signatures. Both the senescence-signature score and specific senescence-associated genes demonstrated an increased capacity to predict mucosal progression, with correct predictions exceeding 97% of cases. Collectively, our findings contribute to a comprehensive understanding of immunosenescence in ATL and suggest that senescence may represent the latest and most important signature of the immunopathogenisis. This highlights its potential value in predicting disease severity.<\/jats:p>","DOI":"10.1093\/cei\/uxae088","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T06:37:07Z","timestamp":1729492627000},"source":"Crossref","is-referenced-by-count":4,"title":["Senescence-related genes are associated with the immunopathology signature of American tegumentary leishmaniasis lesions and may predict progression to mucosal leishmaniasis"],"prefix":"10.1093","volume":"219","author":[{"given":"Carlos Henrique","family":"Fantecelle","sequence":"first","affiliation":[{"name":"N\u00facleo de Doen\u00e7as Infecciosas, Universidade Federal do Esp\u00edrito Santo , Vit\u00f3ria ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"Polaco Covre","sequence":"additional","affiliation":[{"name":"N\u00facleo de Doen\u00e7as Infecciosas, Universidade Federal do Esp\u00edrito Santo , Vit\u00f3ria ,","place":["Brazil"]},{"name":"Division of Medicine , University College London, London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola Oliveira","family":"Lopes","sequence":"additional","affiliation":[{"name":"N\u00facleo de Biotecnologia, Universidade Federal do Esp\u00edrito Santo , Vit\u00f3ria ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabela Valim","family":"Sarmento","sequence":"additional","affiliation":[{"name":"N\u00facleo de Biotecnologia, Universidade Federal do Esp\u00edrito Santo , Vit\u00f3ria ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora","family":"Decote-Ricardo","sequence":"additional","affiliation":[{"name":"Universidade Federal Rural do Rio de Janeiro Departamento de Veterin\u00e1ria, , Rio de Janeiro ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9lio","family":"Geraldo Freire-de-Lima","sequence":"additional","affiliation":[{"name":"Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro , Rio de Janeiro ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert Leonel","family":"de Matos Guedes","sequence":"additional","affiliation":[{"name":"Instituto de Microbiologia Professor Paulo de Goes, Universidade Federal do Rio de Janeiro , Rio de Janeiro ,","place":["Brazil"]},{"name":"Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz , Rio de Janeiro ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria In\u00eas Fernandes","family":"Pimentel","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Infectologia Evandro Chagas, Funda\u00e7\u00e3o Oswaldo Cruz , Rio de Janeiro 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