Localization-Specific Expression of CCR1 and CCR5 by Mast Cell Progenitors.

Maya Salomonsson,Joakim S Dahlin,Jenny Hallgren,Johanna Ungerstedt

doi:10.3389/fimmu.2020.00321

Maya Salomonsson, Joakim S Dahlin + Show 2 more

Open Access

https://doi.org/10.3389/fimmu.2020.00321

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Abstract

Mast cells are powerful immune cells found predominately in barrier tissues. They play an important role in immune surveillance and act as effector cells in allergic reactions. Mast cells develop from mast cell progenitors (MCp), which migrate to the peripheral tissues via the blood circulation. Presumably, the homing of MCp to the peripheral sites and localization is regulated by chemotactic signals. Due to the scarce abundance of these cells, chemotactic receptors have not been previously characterized on primary MCp. Here, mRNA transcripts for CCR1 and CX3CR1 were identified in mouse bone marrow and lung MCp in a gene expression screen of chemotactic receptors. However, surface expression of CCR1 was only found in the bone marrow MCp. Flow cytometry-based screening identified distinct surface expression of CCR5 by mouse peritoneal mast cells and MCp, while surface expression of CXCR2-5, CX3CR1, CCR1-3, CCR6-7, and CCR9 was not detected. Low surface expression of CCR5 was detected in mouse MCp in the bone marrow, spleen, and lung. To translate the findings to human, blood and bone marrow MCp from healthy donors were analyzed for possible CCR1 and CCR5 expression. Human MCp showed distinct surface expression of both CCR1 and CCR5. The expression levels of these chemokine receptors were higher in human bone marrow MCp than in the peripheral blood, suggesting that CCR1 and CCR5 may mediate retention in the bone marrow. In conclusion, mouse and human MCp show differential expression of CCR1 and CCR5 depending on their localization.

Highlights

Mast cells are rare and long-lived tissue-resident immune cells, which play an important role in innate immunity as first-responders in the peripheral tissues, and as potent effector cells by Fc-receptor-mediated activation
Committed mast cell progenitors (MCp) have previously been identified in the bone marrow of C57BL/6 mice [17], but not in BALB/c mice
After four or eight days of culture, the progenies were analyzed by flow cytometry for their surface expression of FcεRI, c-kit, and DX5, referred to as integrin α2 or CD49b

Summary

Introduction

Mast cells are rare and long-lived tissue-resident immune cells, which play an important role in innate immunity as first-responders in the peripheral tissues, and as potent effector cells by Fc-receptor-mediated activation. The first mast cells that populate the tissues derive from progenitors in the yolk sac [1]. Mast cells seem to have a dual origin with long-lived connective tissue type mast cells mainly originating from yolk sac-derived mast cell progenitors (MCp), and mucosal mast cells developing from bone marrow-derived MCp that originate from fetal hematopoietic stem cells [2]. A MCp population is present in peripheral blood and bone marrow [3, 4]. Mouse and human MCp are extremely rare, corresponding to ∼0.005% of blood mononuclear cells [5]. They have a progenitor type morphology with emerging granular structures in the scarce cytoplasm. Mouse MCp are distinguished from mature mast cells by the difference in side scatter (SSC)

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