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

doi:10.1084/jem.20222129

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

Pulmonary Medicine

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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 language	English
Article number	e20222129
Journal	The Journal of experimental medicine
Volume	220
Issue number	6
DOIs	https://doi.org/10.1084/jem.20222129
Publication status	Published - 5 Jun 2023

Bibliographical note

Acknowledgments
Thank you, Ken Murphy, for cleverly referring to this phenomenon as the Pied Piper of Hamelin (DCs) and the following rats (monocytes).
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. Author contributions: K. Rawat, B.N. Lambrecht, A.B. Mara, and C.V. Jakubzick prepared the manuscript; K. Rawat, A. Tewari,
A.B. Mara, W.T. King, S.L. Gibbings, F.W. Kolling, and X. Li executed the experiments; all authors provided intellectual input, critical feedback, discussed results, and designed experiments.

Publisher Copyright: © 2023 Rawat et al.

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title = "CCL5-producing migratory dendritic cells guide CCR5+ monocytes into the draining lymph nodes",

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.",

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

note = "Acknowledgments Thank you, Ken Murphy, for cleverly referring to this phenomenon as the Pied Piper of Hamelin (DCs) and the following rats (monocytes). 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{\textquoteright}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. Author contributions: K. Rawat, B.N. Lambrecht, A.B. Mara, and C.V. Jakubzick prepared the manuscript; K. Rawat, A. Tewari, A.B. Mara, W.T. King, S.L. Gibbings, F.W. Kolling, and X. Li executed the experiments; all authors provided intellectual input, critical feedback, discussed results, and designed experiments. Publisher Copyright: {\textcopyright} 2023 Rawat et al.",

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T1 - CCL5-producing migratory dendritic cells guide CCR5+ monocytes into the draining lymph nodes

AU - Rawat, Kavita

AU - Tewari, Anita

AU - Li, Xin

AU - Mara, Arlind B.

AU - King, William T.

AU - Gibbings, Sophie L.

AU - Nnam, Chinaza F.

AU - Kolling, Fred W.

AU - Lambrecht, Bart N.

AU - Jakubzick, Claudia V.

N1 - Acknowledgments Thank you, Ken Murphy, for cleverly referring to this phenomenon as the Pied Piper of Hamelin (DCs) and the following rats (monocytes). 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. Author contributions: K. Rawat, B.N. Lambrecht, A.B. Mara, and C.V. Jakubzick prepared the manuscript; K. Rawat, A. Tewari, A.B. Mara, W.T. King, S.L. Gibbings, F.W. Kolling, and X. Li executed the experiments; all authors provided intellectual input, critical feedback, discussed results, and designed experiments. Publisher Copyright: © 2023 Rawat et al.

PY - 2023/6/5

Y1 - 2023/6/5

N2 - 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.

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.

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JF - Journal of Experimental Medicine

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ER -

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

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