{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:54:12Z","timestamp":1787169252829,"version":"build-2736575974"},"reference-count":78,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/N013751\/1, MR\/W018748\/1"],"award-info":[{"award-number":["MR\/N013751\/1, MR\/W018748\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"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>Although human lung macrophages are heterogenous and play key roles during health and disease, the mechanisms that govern their activation and function are unclear, particularly in type 2 settings. Our understanding of how human lung macrophages respond to inflammatory signals have predominantly relied on cell lines or peripheral blood derived cells, which have a limited capacity to reflect the complexity of tissue macrophage responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We isolated macrophages from resected human lung tissue and stimulated them ex vivo under type 2 (IL-4, IL-13, or IL-4 + IL-13) or type 1 (IFN\u03b3 + LPS) conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Human lung macrophages stimulated with IL-4\/13, alone or in combination, significantly upregulated expression of the chemokines CCL17, CCL18 and CCL22, along with the transglutaminase TGM2 and the lipoxygenase ALOX15. This type 2 activation profile was distinct from LPS + IFN\u03b3 activated human lung macrophages, which upregulated IL6, IL8, IL1B, TNF\u03b1 and CHI3L1 (YKL-40). Further, type 2 activated human lung macrophage products showed differential metabolic reliance for their induction, with IL-4\/13 induced CCL22 being glycolytically controlled, while ALOX15 was regulated by fatty acid oxidation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These data clarify hallmarks of human lung macrophage activation and polarisation in addition to revealing novel metabolic regulation of type 2 markers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1654717","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T05:26:56Z","timestamp":1760333216000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["The chemokines CCL22 and CCL17 are a defining feature of type 2 stimulated human lung macrophages and exhibit different metabolic dependencies"],"prefix":"10.3389","volume":"16","author":[{"given":"Amanda J. 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