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Recently, we demonstrated that senescent T and NK cells play a role in the establishment and maintenance of this tissue inflammation. Here, we extended those findings using transcriptomic analyses that demonstrate a strong co\u2010induction of senescence and pro\u2010inflammatory gene signatures in cutaneous leishmaniasis (CL) lesions. The senescence\u2010associated signature was characterized by marked expression of key genes such as ATM, Sestrin 2, p16, p21 and p38. The cell type identification from deconvolution of bulk sequencing data showed that the senescence signature was linked with CD8<jats:sup>+<\/jats:sup> effector memory and T<jats:sub>EMRA<\/jats:sub> subsets and also senescent NK cells. A key observation was that the senescence markers in the skin lesions are age\u2010independent of patients and were correlated with lesion size. Moreover, a striking expression of the senescence\u2010associated secretory phenotype (SASP), pro\u2010inflammatory cytokine and chemokines genes was found within lesions that were most strongly associated with the senescent CD8\u00a0T<jats:sub>EMRA<\/jats:sub> subset. Collectively, our results confirm that there is a senescence transcriptomic signature in CL lesions and supports the hypothesis that lesional senescent cells have a major role in mediating immunopathology of the disease.<\/jats:p>","DOI":"10.1111\/imm.13410","type":"journal-article","created":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T18:49:06Z","timestamp":1629917346000},"page":"754-765","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Transcriptomic landscape of skin lesions in cutaneous leishmaniasis reveals a strong CD8<sup>+<\/sup> T cell immunosenescence signature linked to immunopathology"],"prefix":"10.1111","volume":"164","author":[{"given":"Carlos Henrique","family":"Fantecelle","sequence":"first","affiliation":[{"name":"N\u00facleo de Doen\u00e7as Infecciosas Universidade Federal do Esp\u00edrito Santo Vitoria Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana Polaco","family":"Covre","sequence":"additional","affiliation":[{"name":"N\u00facleo de Doen\u00e7as Infecciosas Universidade Federal do Esp\u00edrito Santo Vitoria Brazil"},{"name":"Division of Medicine University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renan","family":"Garcia de Moura","sequence":"additional","affiliation":[{"name":"N\u00facleo de Doen\u00e7as Infecciosas Universidade Federal do Esp\u00edrito Santo Vitoria Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert Leonel de Matos","family":"Guedes","sequence":"additional","affiliation":[{"name":"Instituto de Microbiologia Professor Paulo de Goes Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil"},{"name":"Funda\u00e7\u00e3o Oswaldo Cruz Instituto Oswaldo Cruz Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Farias","family":"Amorim","sequence":"additional","affiliation":[{"name":"Department of Pathobiology School of Veterinary Medicine University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Pathobiology School of Veterinary Medicine University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Mosser","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Genetics University of Maryland College Park Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aloisio","family":"Falqueto","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Social Universidade Federal do Esp\u00edrito Santo Vitoria Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne N.","family":"Akbar","sequence":"additional","affiliation":[{"name":"Division of Medicine University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0663-0981","authenticated-orcid":false,"given":"Daniel Claudio Oliveira","family":"Gomes","sequence":"additional","affiliation":[{"name":"N\u00facleo de Doen\u00e7as Infecciosas Universidade Federal do Esp\u00edrito Santo Vitoria Brazil"},{"name":"N\u00facleo de Biotecnologia Universidade Federal do Esp\u00edrito Santo Vitoria Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"World Health Organization.OMS leishmaniasis. 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