{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T05:19:39Z","timestamp":1761455979326,"version":"build-2065373602"},"reference-count":72,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hirszfeld Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences","award":["6\/2019-2020"],"award-info":[{"award-number":["6\/2019-2020"]}]},{"DOI":"10.13039\/501100009687","name":"Wroclaw Medical University","doi-asserted-by":"crossref","award":["Sub.C140.21.014"],"award-info":[{"award-number":["Sub.C140.21.014"]}],"id":[{"id":"10.13039\/501100009687","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010621","name":"Medical University of Lublin","doi-asserted-by":"crossref","award":["DS 458","DS 460"],"award-info":[{"award-number":["DS 458","DS 460"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Given that we have demonstrated that miR-155-5p is increased in CLL PBMCs and that its reduction with inhibitory siRNA partially restores the immune checkpoint BTLA protein level in CLL B cells, risk stratification for using anti-miR-155-based immunotherapy in CLL seems reasonable, particularly with its potential impact on T cells. Therefore, we aimed to assess the role of miR-155-5p in the epigenetic modification of BTLA levels in CLL T cells, especially since we observed that BTLA expression unfavorably promotes increased proliferative activity and IL-4 secretion in T cells, thus suggesting BTLA malfunction in the CLL T cell subset. Transfection of PBMCs with an inhibitor of miR-155-5p (INH) led to about a ten-fold down-regulation of miR-155-5p levels compared to control siRNA (NC) both in CLL patients and healthy individuals (HC), as assessed by RT-qPCR. Additionally, we did not find any significant differences in BTLA protein expression in T cells after silencing miR-155-5p in either examined group. We demonstrated for the first time that immunotherapy approaches based on systemic administration of anti-miR-155-5p therapeutics would be a favorable strategy in CLL, since they do not affect BTLA expression in T cell populations and could benefit CLL patients with impaired BTLA levels on CLL cells.<\/jats:p>","DOI":"10.3390\/biom15111499","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T07:41:35Z","timestamp":1761291695000},"page":"1499","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["miR-155-5p Silencing Does Not Alter BTLA Molecule Expression in CLL T Cells: Implications for Targeted Immunotherapy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3805-9476","authenticated-orcid":false,"given":"Agata","family":"Kosmaczewska","sequence":"first","affiliation":[{"name":"Laboratory of Immunopathology, Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5135-6336","authenticated-orcid":false,"given":"Lidia","family":"Ciszak","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopathology, Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6098-7554","authenticated-orcid":false,"given":"Anna","family":"Andrzejczak","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Epigenetics of Human Diseases, Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Tomkiewicz","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Epigenetics of Human Diseases, Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4779-1666","authenticated-orcid":false,"given":"Anna","family":"Partyka","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopathology, Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7130-8430","authenticated-orcid":false,"given":"Zofia","family":"Rojek-Gajda","sequence":"additional","affiliation":[{"name":"Dental Center STOMO Clinic, 53-411 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irena","family":"Frydecka","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopathology, Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dariusz","family":"Wo\u0142owiec","sequence":"additional","affiliation":[{"name":"Department and Clinic of Hematology, Blood Neoplasms, and Bone Marrow Transplantation, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Wr\u00f3bel","sequence":"additional","affiliation":[{"name":"Department and Clinic of Hematology, Blood Neoplasms, and Bone Marrow Transplantation, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2340-9442","authenticated-orcid":false,"given":"Agnieszka","family":"Bojarska-Junak","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4841-6120","authenticated-orcid":false,"given":"Jacek","family":"Roli\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8172-0971","authenticated-orcid":false,"given":"Lidia","family":"Karabon","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Epigenetics of Human Diseases, Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental 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