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Here, we investigated inhibitory and activating receptor expression on NK cells in patients with cutaneous leishmaniasis (CL) and explored their phenotypic and functional heterogeneity based on CD57 and NKG2C expression. The expression of CD57 identified NK cells that accumulated in CL patients and exhibited features of senescence. The CD57+ cells exhibited heightened levels of the activating receptor NKG2C and diminished expression of the inhibitory receptor NKG2A. RNA sequencing analyses based on NKG2C transcriptome have revealed two distinct profiles among CL patients associated with cytotoxic and functional genes. The CD57+NKG2C+ subset accumulated in the blood of patients and presented conspicuous features of senescence, including the expression of markers such as p16, yH2ax, and p38, as well as reduced proliferative capacity. In addition, they positively correlated with the number of days until lesion resolution. This study provides a broad understanding of the NK cell biology during Leishmania infection and reinforces the role of senescent cells in the adverse clinical outcomes of CL.<\/jats:p>","DOI":"10.1093\/cei\/uxae040","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T10:44:58Z","timestamp":1714733098000},"page":"279-290","source":"Crossref","is-referenced-by-count":3,"title":["NKG2C+CD57+ natural killer cells with senescent features are induced during cutaneous leishmaniasis and accumulate in patients with lesional healing impairment"],"prefix":"10.1093","volume":"217","author":[{"given":"Luciana Polaco","family":"Covre","sequence":"first","affiliation":[{"name":"N\u00facleo de Doen\u00e7as Infecciosas, Universidade Federal do Esp\u00edrito Santo , Vit\u00f3ria , Brazil"},{"name":"Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro , Rio de Janeiro , Brazil"},{"name":"Division of Medicine, University College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Henrique","family":"Fantecelle","sequence":"additional","affiliation":[{"name":"N\u00facleo de Doen\u00e7as Infecciosas, Universidade Federal do Esp\u00edrito Santo , Vit\u00f3ria , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariadne Mendes","family":"Queiroz","sequence":"additional","affiliation":[{"name":"N\u00facleo de Doen\u00e7as Infecciosas, Universidade Federal do Esp\u00edrito Santo , Vit\u00f3ria , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia Miranda","family":"Fardin","sequence":"additional","affiliation":[{"name":"N\u00facleo de Doen\u00e7as Infecciosas, Universidade Federal do Esp\u00edrito Santo , Vit\u00f3ria , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Henrique","family":"Miranda","sequence":"additional","affiliation":[{"name":"N\u00facleo de Biotecnologia, Universidade Federal do Esp\u00edrito Santo , Vit\u00f3ria , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sian","family":"Henson","sequence":"additional","affiliation":[{"name":"Translational Medicine and Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra Marcia da","family":"Fonseca-Martins","sequence":"additional","affiliation":[{"name":"Instituto de Microbiologia Professor Paulo de Goes, Universidade Federal do Rio de Janeiro , Rio de Janeiro , 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 , Brazil"},{"name":"Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz , Rio de Janeiro , 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