CCL5-producing Migratory Dendritic Cells Guide CCR5+ Monocytes into the Draining Lymph Nodes

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2023 Mar 22

PMID 36946983

Authors

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

Affiliations

Soon will be listed here.

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.

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