{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:44:02Z","timestamp":1791398642630,"version":"4.3.3"},"reference-count":84,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"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>Severe and overlapping asthma endotypes\u2014particularly steroid-insensitive disease\u2014remain undertreated, highlighting the need for a T-cell\u2013centered synthesis. This review frames asthma heterogeneity through the interplay of T-cell axes, with Th2 pathways shaping T2-high disease and Th17\/Treg imbalance characterizing T2-low features and much of steroid resistance. Building on this framework, we map therapies to mechanism: IL-4R\u03b1 and IL-5\/IL-5R blockade chiefly mitigate Th2-dominated circuits, whereas upstream alarmin inhibition (e.g., TSLP) modulates epithelial\u2013immune cues that influence both T2-high biology and selected T2-low processes. We then outline what is needed to translate mechanisms into decisions\u2014integrated biomarkers to refine endotypes and mechanism-guided switching or combinations, with emphasis on T2-low populations where unmet need is greatest. By linking T-cell biology to therapeutic leverage points, the review offers a concise path from mechanism to patient stratification and more rational treatment choices.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1658774","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T06:36:09Z","timestamp":1765434969000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["T cell heterogeneity in asthma pathogenesis: from immunological mechanisms to biological targeted 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