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In experimental models, short-lived Th2 effector cells and type 2 innate lymphocytes (ILC2) contribute to acute type 2 inflammation, yet the cellular architecture that drives chronic type 2 inflammation and prevents exhaustion remains poorly understood. To define the Th2 landscape in chronic type 2 inflammation, we established a mouse model of long-term pulmonary allergen exposure and found that type 2 inflammation was broadly sustained over at least 4 months despite chronic stimulation. Th2 cells in the lung parenchyma during chronic inflammation were distinct from acute inflammation and resting memory phases, and included an expanded T cell factor-1 (TCF1)-expressing progenitor-like Th2 population. Tissue Th2 progenitors were absent in the nose and in helminth infections, suggesting that type 2 immunopathology is context-specific. Transcriptomic deconstruction of acute and chronic pulmonary Th2 responses defined divergent effector programs as well as the transcriptional signature of a tissue Th2 memory population that resembled human Th2 progenitors. Integrated transcriptomic analysis comparing type 2 inflammation to chronic viral infection revealed a distinct stemness module underlying chronic Th2 inflammation that was separable from a common core memory module.\n                  <jats:italic>In vivo<\/jats:italic>\n                  , lung Th2 progenitors coupled self-renewal with effector cell differentiation and could be sustained for weeks without antigen persistence or contribution from the lymph node. Maintenance of Th2 progenitors was partially dependent on lung parenchymal B cells and associated with bronchus-associated lymphoid tissue formation. Moreover, Th2 progenitors, in contrast to Th2 effectors and ILC2s, were sufficient to both initiate and sustain type 2 inflammation. Thus, we define tissue Th2 progenitors as a distinct cellular state that arises during chronic type 2 inflammation and establish the central role of these cells in maintaining the architecture of Th2 responses over time.\n                <\/jats:p>","DOI":"10.1101\/2025.10.03.680133","type":"posted-content","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T03:45:13Z","timestamp":1759722313000},"source":"Crossref","is-referenced-by-count":0,"title":["Progenitor T cells drive chronic pulmonary type 2 inflammation"],"prefix":"10.64898","author":[{"given":"Radomir","family":"Kratchmarov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojiong","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Nagai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinan","family":"Alhallak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juying","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunli","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"von Moltke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua A.","family":"Boyce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick J.","family":"Brennan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025100813201269000_2025.10.03.680133v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.07.015"},{"key":"2025100813201269000_2025.10.03.680133v1.2","doi-asserted-by":"crossref","unstructured":"Chen, T. , et al. 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