{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:35:53Z","timestamp":1774647353866,"version":"3.50.1"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"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:p>Hashimoto\u2019s thyroiditis (HT) is one of the most common organ-specific autoimmune diseases, characterized by chronic thyroid gland inflammation. Helper T (Th) CD4<jats:sup>+<\/jats:sup> cells, whose surface receptors are highly glycosylated, are involved in the pathomechanism of HT. Our study aimed to characterize <jats:italic>N<\/jats:italic>-glycosylation profiles in two pools of CD4<jats:sup>+<\/jats:sup> T cells, defined by the expression of CD25<jats:sup>+<\/jats:sup> late activation marker (CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>) and CD25-negative cells (CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>-<\/jats:sup>) in HT. Two study groups were recruited: HT1 with elevated thyroid autoantibodies and TSH level within the normal range without hypothyroidism, and HT2, hypothyroid HT patients, adequately metabolically controlled while on L-thyroxine replacement therapy, and healthy subjects to the control group (CTR). <jats:italic>N<\/jats:italic>-glycans from CD4<jats:sup>+<\/jats:sup> cell proteins, released using <jats:italic>N<\/jats:italic>-glycosidase F, were analyzed by MALDI-Tof mass spectrometry. RT-qPCR was used to determine the expression of selected glycogenes. We found significant differences in the glycome of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>-<\/jats:sup> and CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> cells. In homeostasis (CTR), a predominance of complex-type glycans was observed in CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>-<\/jats:sup> cells, whereas the oligomannose-type structures prevail in CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> lymphocytes. In autoimmunity and progressive thyroid dysfunction, the rearrangement of <jats:italic>N<\/jats:italic>-glycans in Th cells was observed, in opposite directions in the CD4<jats:sup>+<\/jats:sup> pools. Complex-type structures are replaced by oligomannose forms in CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>-<\/jats:sup> in the HT1 group, while in HT2, a restoration of glycosylation profile to the level of CTR was detected. CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> cells accelerated complex-type synthesis in HT1, which was normalized in HT2 patients. Changes in the profile of <jats:italic>N<\/jats:italic>-linked glycans are partially reflected in the expression of mannosidases and glycosyltransferases. Our study demonstrates for the first time the diverse <jats:italic>N<\/jats:italic>-glycosylation profiles in CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>-<\/jats:sup> and CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> cells, and the rearrangement of <jats:italic>N<\/jats:italic>-glycan structures specific for each pool of Th cells in HT. Further studies are needed to determine the functional aspect of the identified <jats:italic>N<\/jats:italic>-glycosylation changes during thyroid autoimmunity.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1633344","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T05:29:01Z","timestamp":1757914141000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The diverse N-glycosylation profiles of CD4+CD25- and CD4+CD25+ T cells in Hashimoto\u2019s 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