CCL5-producing migratory dendritic cells guide CCR5+ monocytes into the draining lymph nodes.

Autor: Rawat K; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Hanover, NH, USA., Tewari A; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Hanover, NH, USA., Li X; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Hanover, NH, USA., Mara AB; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Hanover, NH, USA., King WT; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Hanover, NH, USA., Gibbings SL; Department of Pediatrics, National Jewish Health , Denver, CO, USA., Nnam CF; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Hanover, NH, USA., Kolling FW; Dartmouth Cancer Center, Dartmouth Geisel School of Medicine , Lebanon, NH, USA., Lambrecht BN; Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research , Ghent, Belgium.; Department of Internal Medicine and Pediatrics, Ghent University , Ghent, Belgium.; Department of Pulmonary Medicine, Erasmus MC , Rotterdam, Netherlands., Jakubzick CV; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Hanover, NH, USA.
Jazyk: angličtina
Zdroj: The Journal of experimental medicine [J Exp Med] 2023 Jun 05; Vol. 220 (6). Date of Electronic Publication: 2023 Mar 22.
DOI: 10.1084/jem.20222129
Abstrakt: 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.
(© 2023 Rawat et al.)
Databáze: MEDLINE