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Upon their activation, antigen-bearing cDCs migrate from peripheral tissue to regional lymph nodes (LNs) in a manner dependent on the chemokine receptor, CCR7. To maintain immune homeostasis, these departing cDCs must be replenished by new cDCs that develop from pre-DCs, but the molecular signals that direct pre-DC trafficking from the BM to the blood and peripheral tissues remain poorly understood. In the present study, we found that pre-DCs express the chemokine receptors CXCR4, CCR2, and CX3CR1, and that each of these receptors has a distinct role in pre-DC trafficking. Flow cytometric analysis of pre-DCs lacking CXCR4 revealed that this receptor is required for the retention of pre-DCs in the BM. Analyses of mice lacking CCR2 or CX3CR1, or both, revealed that they promote pre-DC migration to the lung at steady state. CCR2, but not CX3CR1, was required for pre-DC migration to the inflamed lung. Thus, these multiple chemokine receptors cooperate in a step-wise fashion to coordinate the trafficking of pre-DCs from the BM to the circulation and peripheral tissues.<\/jats:p>","DOI":"10.1189\/jlb.1a0616-285r","type":"journal-article","created":{"date-parts":[[2017,2,1]],"date-time":"2017-02-01T20:30:21Z","timestamp":1485981021000},"page":"1143-1153","source":"Crossref","is-referenced-by-count":65,"title":["Distinct functions of CXCR4, CCR2, and CX3CR1 direct dendritic cell precursors from the bone marrow to the lung"],"prefix":"10.1093","volume":"101","author":[{"given":"Hideki","family":"Nakano","sequence":"first","affiliation":[{"name":"Immunity, Inflammation, and Disease Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health , Research Triangle Park, North Carolina , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miranda R","family":"Lyons-Cohen","sequence":"additional","affiliation":[{"name":"Immunity, Inflammation, and Disease Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health , Research Triangle Park, North Carolina , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory S","family":"Whitehead","sequence":"additional","affiliation":[{"name":"Immunity, Inflammation, and Disease Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health , Research Triangle Park, North Carolina , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Nakano","sequence":"additional","affiliation":[{"name":"Immunity, Inflammation, and Disease Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health , Research Triangle Park, North Carolina , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald N","family":"Cook","sequence":"additional","affiliation":[{"name":"Immunity, Inflammation, and Disease Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health , Research Triangle Park, North Carolina , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,2,1]]},"reference":[{"key":"2023011712222493100_B1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/32588","article-title":"Dendritic cells and the control of immunity","volume":"392","author":"Banchereau","year":"1998","journal-title":"Nature"},{"key":"2023011712222493100_B2","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/j.cell.2011.08.010","article-title":"SnapShot: dendritic cells","volume":"146","author":"Idoyaga","year":"2011","journal-title":"Cell"},{"key":"2023011712222493100_B3","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/S0140-6736(10)61226-3","article-title":"The role of dendritic and epithelial cells as master regulators of allergic airway inflammation","volume":"376","author":"Lambrecht","year":"2010","journal-title":"Lancet"},{"key":"2023011712222493100_B4","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1084\/jem.193.1.51","article-title":"Specific migratory dendritic cells rapidly transport antigen from the airways to the thoracic lymph nodes","volume":"193","author":"Vermaelen","year":"2001","journal-title":"J. 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