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Circulating monocytes are generally viewed as central precursors of these tissue effector macrophages. Here, we provide evidence that granulomas derive from alveolar macrophages serving as a local reservoir for the expansion of activated phagocytic macrophages. By exploring lung granulomatous responses to silica particles in <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u2010deficient mice, we found that the absence of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b1, but not <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2, was associated with reduced <jats:styled-content style=\"fixed-case\">CD11b<jats:sup>high<\/jats:sup><\/jats:styled-content> phagocytic macrophage accumulation and fewer granulomas. This defect was associated with impaired alveolar clearance and resulted in the development of pulmonary alveolar proteinosis (<jats:styled-content style=\"fixed-case\">PAP<\/jats:styled-content>). Reconstitution of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b1<jats:sup>\u2212\/\u2212<\/jats:sup> mice with recombinant <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b1 restored lung clearance functions and the pulmonary accumulation of <jats:styled-content style=\"fixed-case\">CD11b<jats:sup>high<\/jats:sup><\/jats:styled-content> phagocytic macrophages. Mechanistically, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b1 induced the proliferation of <jats:styled-content style=\"fixed-case\">CD11b<jats:sup>low<\/jats:sup><\/jats:styled-content> alveolar macrophages and differentiated these cells into <jats:styled-content style=\"fixed-case\">CD11b<jats:sup>high<\/jats:sup><\/jats:styled-content> macrophages which perform critical phagocytic functions and organize granuloma. We newly discovered here that <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b1 triggers lung responses requiring macrophage proliferation and maturation from tissue\u2010resident macrophages. Copyright \u00a9 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4487","type":"journal-article","created":{"date-parts":[[2014,11,25]],"date-time":"2014-11-25T04:14:15Z","timestamp":1416888855000},"page":"698-709","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["<scp>IL<\/scp>\u20101\u03b1 induces <scp>CD11b<sup>low<\/sup><\/scp> alveolar macrophage proliferation and maturation during granuloma formation"],"prefix":"10.1002","volume":"235","author":[{"given":"Fran\u00e7ois","family":"Huaux","sequence":"first","affiliation":[{"name":"Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Experimentale et Clinique (IREC) Universit\u00e9 catholique de Louvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Lo Re","sequence":"additional","affiliation":[{"name":"Louvain Centre for Toxicology and Applied Pharmacology (LTAP), 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