PMID- 36946983 OWN - NLM STAT- MEDLINE DCOM- 20230324 LR - 20230505 IS - 1540-9538 (Electronic) IS - 0022-1007 (Print) IS - 0022-1007 (Linking) VI - 220 IP - 6 DP - 2023 Jun 5 TI - CCL5-producing migratory dendritic cells guide CCR5+ monocytes into the draining lymph nodes. LID - 10.1084/jem.20222129 [doi] LID - e20222129 AB - Dendritic cells (DCs) and monocytes capture, transport, and present antigen to cognate T cells in the draining lymph nodes (LNs) in a CCR7-dependent manner. Since only migratory DCs express this chemokine receptor, it is unclear how monocytes reach the LN. In steady-state and following inhalation of several PAMPs, scRNA-seq identified LN mononuclear phagocytes as monocytes, resident, or migratory type 1 and type 2 conventional (c)DCs, despite the downregulation of Xcr1, Clec9a, H2-Ab1, Sirpa, and Clec10a transcripts on migratory cDCs. Migratory cDCs, however, upregulated Ccr7, Ccl17, Ccl22, and Ccl5. Migratory monocytes expressed Ccr5, a high-affinity receptor for Ccl5. Using two tracking methods, we observed that both CD88hiCD26lomonocytes and CD88-CD26hi cDCs captured inhaled antigens in the lung and migrated to LNs. Antigen exposure in mixed-chimeric Ccl5-, Ccr2-, Ccr5-, Ccr7-, and Batf3-deficient mice demonstrated that while antigen-bearing DCs use CCR7 to reach the LN, monocytes use CCR5 to follow CCL5-secreting migratory cDCs into the LN, where they regulate DC-mediated immunity. CI - (c) 2023 Rawat et al. FAU - Rawat, Kavita AU - Rawat K AUID- ORCID: 0000-0002-8302-9890 AD - Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Hanover, NH, USA. FAU - Tewari, Anita AU - Tewari A AUID- ORCID: 0000-0001-6331-1701 AD - Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Hanover, NH, USA. FAU - Li, Xin AU - Li X AUID- ORCID: 0000-0002-2050-2628 AD - Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Hanover, NH, USA. FAU - Mara, Arlind B AU - Mara AB AUID- ORCID: 0000-0001-9823-5243 AD - Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Hanover, NH, USA. FAU - King, William T AU - King WT AUID- ORCID: 0000-0003-2312-6207 AD - Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Hanover, NH, USA. FAU - Gibbings, Sophie L AU - Gibbings SL AUID- ORCID: 0000-0001-9623-0705 AD - Department of Pediatrics, National Jewish Health , Denver, CO, USA. FAU - Nnam, Chinaza F AU - Nnam CF AUID- ORCID: 0000-0001-6230-6169 AD - Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Hanover, NH, USA. FAU - Kolling, Fred W AU - Kolling FW AUID- ORCID: 0000-0002-6178-9901 AD - Dartmouth Cancer Center, Dartmouth Geisel School of Medicine , Lebanon, NH, USA. FAU - Lambrecht, Bart N AU - Lambrecht BN AUID- ORCID: 0000-0003-4376-6834 AD - Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research , Ghent, Belgium. AD - Department of Internal Medicine and Pediatrics, Ghent University , Ghent, Belgium. AD - Department of Pulmonary Medicine, Erasmus MC , Rotterdam, Netherlands. FAU - Jakubzick, Claudia V AU - Jakubzick CV AUID- ORCID: 0000-0002-3731-0198 AD - Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Hanover, NH, USA. LA - eng GR - R01 HL135001/HL/NHLBI NIH HHS/United States GR - S10 OD025235/OD/NIH HHS/United States GR - R01 HL115334/HL/NHLBI NIH HHS/United States GR - S10 OD030242/OD/NIH HHS/United States GR - P20 GM130454/GM/NIGMS NIH HHS/United States GR - P30 CA023108/CA/NCI NIH HHS/United States GR - R35 HL155458/HL/NHLBI NIH HHS/United States GR - 789384/ERC_/European Research Council/International GR - T32 AI007363/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20230322 PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (Receptors, CCR7) RN - 0 (Antigens) SB - IM MH - Mice MH - Animals MH - *Monocytes MH - *Dendritic Cells MH - Receptors, CCR7 MH - Lung MH - Antigens MH - Lymph Nodes MH - Cell Movement MH - Mice, Inbred C57BL PMC - PMC10072223 COIS- Disclosures: The authors declare no competing interests exist. EDAT- 2023/03/23 06:00 MHDA- 2023/03/25 06:00 PMCR- 2023/03/22 CRDT- 2023/03/22 11:02 PHST- 2022/12/12 00:00 [received] PHST- 2023/02/10 00:00 [revised] PHST- 2023/03/08 00:00 [accepted] PHST- 2023/03/22 11:02 [entrez] PHST- 2023/03/23 06:00 [pubmed] PHST- 2023/03/25 06:00 [medline] PHST- 2023/03/22 00:00 [pmc-release] AID - 213962 [pii] AID - jem.20222129 [pii] AID - 10.1084/jem.20222129 [doi] PST - ppublish SO - J Exp Med. 2023 Jun 5;220(6):e20222129. doi: 10.1084/jem.20222129. Epub 2023 Mar 22.