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

Kavita Rawat, Anita Tewari, Xin Li, Arlind B. Mara, William T. King, Sophie L. Gibbings, Chinaza F. Nnam, Fred W. Kolling, Bart N. Lambrecht, Claudia V. Jakubzick

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17 Citations (Scopus)
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Abstract

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.

Original languageEnglish
Article numbere20222129
JournalThe Journal of experimental medicine
Volume220
Issue number6
DOIs
Publication statusPublished - 5 Jun 2023

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health (NIH) grants R01 HL115334, R01 HL135001, and R35 HL155458 (C.V. Jakubzick). A.B. Mara is supported by NIH T32AI007363. B.N. Lambrecht is supported by a Research Foundation – Flanders Methusalem grant (contract 01M01521), a Research Foundation – Flanders Excellence of Science grant (contract 3GOH1222), and a European Research Council grant under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 789384, contract no. 01Z00110). Single-cell studies were conducted through the Dartmouth Center for Quantitative Biology in collaboration with the Genomics and Molecular Biology Shared Resource (supported by National Cancer Institute Cancer Center Support Grant 5P30CA023108 and NIH S10 1S10OD030242 awards) with support from National Institute of General Medical Sciences P20GM130454 and NIH S10 S10OD025235 awards.

Publisher Copyright:
© 2023 Rawat et al.

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