{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T06:08:59Z","timestamp":1789711739527,"version":"4.0.1"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Dermatomyositis (DM), particularly the anti-TIF1\u03b3\u2011positive subtype, is associated with a substantially elevated risk of malignancy. However, the peripheral immune landscape of this autoantibody-defined subset, especially in patients without concurrent cancer, remains incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed single\u2011cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from five patients with anti\u2011TIF1\u03b3\u2011positive DM (the subtype with the highest malignancy risk) and compared their profiles with those of two other DM subtypes: anti\u2011MDA5\u2011positive DM (intermediate malignancy risk) and anti\u2011synthetase syndrome (ASyS, low malignancy risk).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All three subtypes exhibited profound immune remodeling, characterized by reduced frequencies of cytotoxic lineage cells. Anti\u2011TIF1\u03b3\u2011positive DM showed a compensatory shift toward humoral immunity, with increased B\u2011lineage cells, whereas classical monocyte elevation was specific to the anti\u2011MDA5\u2011positive DM and ASyS subtypes. Notably, anti\u2011TIF1\u03b3\u2011positive DM was uniquely distinguished by an increased frequency of immunosuppressive regulatory T (Treg) cells, a finding validated by immunohistochemistry in patient skin tissue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These results delineate a peripheral immunological signature of anti\u2011TIF1\u03b3\u2011positive DM, marked by compromised cytotoxic surveillance, aberrant humoral responses, and selective Treg enrichment. We hypothesize that this Treg elevation may contribute to an immunosuppressive milieu that favors malignancy, although this mechanism remains speculative and requires functional validation in prospective cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1921818","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:38:58Z","timestamp":1789709938000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dysregulation of the cytotoxic-humoral axis and expansion of regulatory T cells in anti-TIF1\u03b3- positive dermatomyositis"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaoguang","family":"Cui","sequence":"first","affiliation":[{"name":"National-Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi\u2019an Jiaotong University","place":["Xi\u2019an, China"]},{"name":"Department of Rheumatology 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