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Men with LOY have increased risks of all-cause mortality and the major causes of death, including many forms of cancer. It has been suggested that the association between LOY and disease risk depends on what type of leukocyte is affected with Y loss, with prostate cancer patients showing higher levels of LOY in CD4\u2009+\u2009T lymphocytes. In previous studies, Y loss has however been observed at relatively low levels in this cell type. This motivated us to investigate whether specific subsets of CD4\u2009+\u2009T lymphocytes are particularly affected by LOY. Publicly available, T lymphocyte enriched, single-cell RNA sequencing datasets from patients with liver, lung or colorectal cancer were used to study how LOY affects different subtypes of T lymphocyte. To validate the observations from the public data, we also generated a single-cell RNA sequencing dataset comprised of 23 PBMC samples and 32 CD4\u2009+\u2009T lymphocytes enriched samples.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Regulatory T cells had significantly more LOY than any other studied T lymphocytes subtype. Furthermore, LOY in regulatory T cells increased the ratio of regulatory T cells compared with other T lymphocyte subtypes, indicating an effect of Y loss on lymphocyte differentiation. This was supported by developmental trajectory analysis of CD4\u2009+\u2009T lymphocytes culminating in the regulatory T cells cluster most heavily affected by LOY. Finally, we identify dysregulation of 465 genes in regulatory T cells with Y loss, many involved in the immunosuppressive functions and development of regulatory T cells.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Here, we show that regulatory T cells are particularly affected by Y loss, resulting in an increased fraction of regulatory T cells and dysregulated immune functions. Considering that regulatory T cells plays a critical role in the process of immunosuppression; this enrichment for regulatory T cells with LOY might contribute to the increased risk for cancer observed among men with Y loss in leukocytes.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12864-024-10168-7","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T07:01:58Z","timestamp":1709622118000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Loss of chromosome Y in regulatory T cells"],"prefix":"10.1186","volume":"25","author":[{"given":"Jonas","family":"Mattisson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonatan","family":"Halvardson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo\u017cena","family":"Bruhn-Olszewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"Olszewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Danielsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefin","family":"Bjurling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Lindberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ammar","family":"Zaghlool","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edyta","family":"Rychlicka-Buniowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan P.","family":"Dumanski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars A.","family":"Forsberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,5]]},"reference":[{"key":"10168_CR1","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1038\/nrg.2016.145","volume":"18","author":"LA Forsberg","year":"2017","unstructured":"Forsberg LA, Gisselsson D, Dumanski JP. 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The research was approved by the local research ethics committee in Uppsala, Sweden Dnr. 2015\/458 (EpiHealth cohort), amendment Dnr. 2015\/458\/2 (UCAN cohort), Dnr. 2015\/092 (UAD cohort).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"J.P.D. and L.A.F. are cofounders and shareholders in Cray Innovation AB. The remaining authors declare no competing interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"243"}}