{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:55:32Z","timestamp":1791860132760,"version":"4.3.4"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":90,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017819","name":"Hull York Medical School","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017819","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Biotechnology and Biological Sciences Research Council White Rose","award":["BB\/J014443\/1"],"award-info":[{"award-number":["BB\/J014443\/1"]}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/W018578\/1"],"award-info":[{"award-number":["MR\/W018578\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Identifying cell intrinsic regulators of immune sexual dimorphism is critical for treatment of several immunopathologies. We show that Malat1 is required for appropriate cytokine expression in female but not male T helper 2 (Th2) cells. Malat1 deficiency impairs in vitro Th2 differentiation of na\u00efve CD4+ T cells from female mice, characterized by transcriptome-wide effects and suppression of cytokine expression, particularly interleukin (IL)-10. Upon IL-10 receptor (IL10R) blockade a pronounced effect is also seen on IL-4 and IL-13. Mechanistically, na\u00efve CD4+ T cells from Malat1\u2212\/\u2212 female mice demonstrate altered early activation kinetics and impaired early differentiation gene expression, including upregulation of an interferon-stimulated gene (ISG) module. This is followed by suppression of IL2R\u03b1 and IL2R\u03b3 expression and IL-2\u2013mediated differentiation. Mimicking the effect of Malat1 loss by maintaining early ISG expression in WT cells with interferon \u03b2 treatment partially phenocopies the effects of Malat1 deficiency. A subset of the effects of Malat1 loss in female cells is also observed in male cells. However, this does not affect endpoint Th2 differentiation. Male CD4+ T cells demonstrate stronger early activation, higher ISG expression during early differentiation, maintenance of IL2R\u03b1 expression independently of Malat1, and lower sensitivity to exogenous IL-2 during late differentiation compared with female cells. In vivo, female, but not male, Malat1\u2212\/\u2212 mice demonstrate altered Th2 cytokine expression characterized by a reduction in IL-10+ Th2 cells in both lung and spleen following priming and challenge with Schistosoma mansoni eggs, a model of lung type 2 inflammation. Overall, these findings reveal Malat1 as a novel determinant of immune sexual dimorphism.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf177","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:13:08Z","timestamp":1756339988000},"page":"2947-2960","source":"Crossref","is-referenced-by-count":3,"title":["<i>Malat1<\/i>\n                    regulates female Th2 cell cytokine expression through controlling early differentiation and response to IL-2"],"prefix":"10.1093","volume":"214","author":[{"given":"Mags","family":"Gwynne","sequence":"first","affiliation":[{"name":"Hull York Medical School, University of York , York,","place":["United Kingdom"]},{"name":"York Biomedical Research Institute, University of York , York,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie A","family":"West","sequence":"additional","affiliation":[{"name":"Hull York Medical School, University of York , York,","place":["United 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