The chemokine receptor CCR2 maintains plasmacytoid dendritic cell homeostasis

Oriane Cédile; Line Østerby Jørgensen; Ida Frank; Agnieszka Wlodarczyk; Trevor Owens

doi:10.1016/j.imlet.2017.10.012

The chemokine receptor CCR2 maintains plasmacytoid dendritic cell homeostasis

Immunol Lett. 2017 Dec:192:72-78. doi: 10.1016/j.imlet.2017.10.012. Epub 2017 Oct 26.

Authors

Oriane Cédile¹, Line Østerby Jørgensen², Ida Frank³, Agnieszka Wlodarczyk⁴, Trevor Owens⁵

Affiliations

¹ Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, J.B. Winsløwsvej 25, 5000 Odense C, Denmark. Electronic address: oriane.cedile@rsyd.dk.
² Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, J.B. Winsløwsvej 25, 5000 Odense C, Denmark. Electronic address: linej12@student.sdu.dk.
³ Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, J.B. Winsløwsvej 25, 5000 Odense C, Denmark. Electronic address: idafrank@jubii.dk.
⁴ Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, J.B. Winsløwsvej 25, 5000 Odense C, Denmark. Electronic address: awlodarczyk@health.sdu.dk.
⁵ Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, J.B. Winsløwsvej 25, 5000 Odense C, Denmark. Electronic address: towens@health.sdu.dk.

PMID: 29106985
DOI: 10.1016/j.imlet.2017.10.012

Abstract

Thymic dendritic cells (DC) play a role in central tolerance. Three thymic DC subtypes have been described: plasmacytoid DC (pDC) and two conventional DC (cDC), CD8α⁺ Sirpα^- DC and Sirpα⁺ CD8α^- cDC. Both pDC and Sirpα⁺ cDC can take up antigen in periphery and migrate into the thymus in response to chemokine signaling via CCR9 and CCR2 respectively. CCL2 is a major ligand for CCR2 and we previously showed that it was constitutively expressed in thymus, and that mice overexpressing CCL2 in thymus had reduced numbers of autoreactive T cells but elevated numbers of pDC. We have here investigated the role of CCL2-CCR2 axis in thymic pDC migration. We found that pDC expressed CCR2 at a high level and that their frequency was decreased in thymus, spleen and inguinal lymph nodes in mice lacking CCR2, but not in mice lacking CCL2. pDC migration towards the cortex or medulla within the thymus was not affected by CCL2 or CCR2 deficiency. Although some thymic progenitors expressed CCR2, this did not include those that give rise to pDC. Based on these results, we propose that CCR2 is involved in pDC homeostasis but its ligand CCL2 does not play a major role.

Keywords: CCL2; CCR2; Chemokine; Plasmacytoid dendritic cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation
Cell Movement
Cell Proliferation
Cells, Cultured
Chemokine CCL2 / genetics
Dendritic Cells / immunology*
Female
Homeostasis
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, CCR2 / genetics
Receptors, CCR2 / metabolism*
T-Lymphocytes / immunology*
Thymus Gland / immunology*

Substances

Ccr2 protein, mouse
Chemokine CCL2
Receptors, CCR2