{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T22:39:59Z","timestamp":1761172799636,"version":"build-2065373602"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI183392, AI149456, AI136862"],"award-info":[{"award-number":["AI183392, AI149456, AI136862"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Cutaneous leishmaniasis (CL) is an infectious disease characterized by severe local inflammatory response, predominantly mediated by cytokines such as IL-1\n                    <jats:italic>\u03b2<\/jats:italic>\n                    and TNF, and cytotoxicity, contributing to tissue damage and lesion development. Given the high rate of therapeutic failure in\n                    <jats:italic>Leishmania braziliensis<\/jats:italic>\n                    transmission areas, the investigation of molecules that regulate inflammatory response has become a promising adjuvant therapeutical strategy. In this study we investigated the effects of Annexin A1 (ANXA1) on the inflammatory response of CL patients. We initially performed\n                    <jats:italic>in silico<\/jats:italic>\n                    analyses from our previous transcriptome databases and found increased expression of\n                    <jats:italic>ANXA1, IL1B<\/jats:italic>\n                    , and\n                    <jats:italic>IL10<\/jats:italic>\n                    genes in skin biopsies from CL patients when compared to healthy skin from healthy subjects (HS). Also, increased levels of ANXA1, IL1\n                    <jats:italic>\u03b2<\/jats:italic>\n                    , and IL10 proteins were observed in serum levels and cultures of skin biopsies in CL patients when compared to HS. Treatment of lesion biopsies with recombinant ANXA1 reduced IL-1\n                    <jats:italic>\u03b2<\/jats:italic>\n                    levels without affecting IL-10 secretion, indicating a selective anti-inflammatory effect. Additionally, monocyte-derived macrophages from HS increased ANXA1, IL-1\n                    <jats:italic>\u03b2<\/jats:italic>\n                    , and IL-10 production upon\n                    <jats:italic>Leishmania<\/jats:italic>\n                    infection. Blockade of FPR2 receptor increased ANXA1 levels. Finally, addition of recombinant ANXA1 to macrophages did not affect the ability of these cells to kill\n                    <jats:italic>Leishmania<\/jats:italic>\n                    . Our findings demonstrate that ANXA1 negatively regulates IL-1\n                    <jats:italic>\u03b2<\/jats:italic>\n                    in CL, without impairing anti-inflammatory mechanisms or macrophage microbicidal activity, highlighting its potential use as an adjuvant therapy for controlling inflammation and disease progression.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1685264","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T05:31:30Z","timestamp":1761111090000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Annexin A1 downregulates in vitro IL-1\u03b2 production in L. braziliensis-infected cells"],"prefix":"10.3389","volume":"16","author":[{"given":"Camila P.","family":"Santos","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauricio 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