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Mast cell progenitors: Origin, development and migration to tissues

Dahlin, Joakim S., Hallgren, Jenny·2015·Molecular Immunology
DOI 10.1016/j.molimm.2014.01.018
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Fig. 1 Proposed model for the development of MCp. Mast cells originate from the bone marrow where they develop from the hematopoietic stem cells (HSC) via multipotent progenitors (MPP), common myeloid progenitors (CMPs) and granulocyte/monocyte progenitors (GMPs). Progenitors giving rise to both mast cells and basophils have been isolated from bone marrow within the GMP fraction. The majority of these progenitors are found among the Fc 𝛆 RI + GMPs. However, progenitors that give rise to mast cells and basophils are also found within the Fc 𝛆 RI -GMPs. Bipotent basophil/mast cell progenitors (BMCPs) in the spleen are largely negative for Fc 𝛆 RI expression in C57BL mice, consistent with the Fc 𝛆 RI -GMPs in bone marrow. Committed MCp can either lack or express Fc 𝛆 RI in the bone marrow. Therefore, they likely develop from both Fc 𝛆 RI -and Fc 𝛆 RI + GMPs. MCp exit the bone marrow as Fc 𝛆 RI -and Fc 𝛆 RI + cells that can be found in the blood from BALB/c and C57BL mice as committed MCp. In the peripheral tissues MCp express Fc 𝛆 RI at low levels in C57BL mice. The numbers in superscript at each progenitor stage is repeated in the yellow box to describe the surface markers used to define the particular progenitor stage.
Fig. 1 Proposed model for the development of MCp. Mast cells originate from the bone marrow where they develop from the hematopoietic stem cells (HSC) via multipotent progenitors (MPP), common myeloid progenitors (CMPs) and granulocyte/monocyte progenitors (GMPs). Progenitors giving rise to both mast cells and basophils have been isolated from bone marrow within the GMP fraction. The majority of these progenitors are found among the Fc 𝛆 RI + GMPs. However, progenitors that give rise to mast cells and basophils are also found within the Fc 𝛆 RI -GMPs. Bipotent basophil/mast cell progenitors (BMCPs) in the spleen are largely negative for Fc 𝛆 RI expression in C57BL mice, consistent with the Fc 𝛆 RI -GMPs in bone marrow. Committed MCp can either lack or express Fc 𝛆 RI in the bone marrow. Therefore, they likely develop from both Fc 𝛆 RI -and Fc 𝛆 RI + GMPs. MCp exit the bone marrow as Fc 𝛆 RI -and Fc 𝛆 RI + cells that can be found in the blood from BALB/c and C57BL mice as committed MCp. In the peripheral tissues MCp express Fc 𝛆 RI at low levels in C57BL mice. The numbers in superscript at each progenitor stage is repeated in the yellow box to describe the surface markers used to define the particular progenitor stage.CC-BY-NC-ND · From the PDF
Fig. 2 Representation of transcription factors involved in the mast cell lineage commitment. GMPs, which express C/EBP 𝛂 , turn on GATA-2 to become eosinophil progenitors (EoP). To form a progenitor with mast cell (MC) and basophil (Ba) potency, C/EBP 𝛂 is downregulated in the GMP along with upregulation of GATA2, GATA-3 and Hes-1. For MCp commitment, MITF is upregulated and C/EBP 𝛂 is further downregulated whereas for basophil progenitor (BaP) commitment MITF is downregulated and C/EBP 𝛂 is upregulated.
Fig. 2 Representation of transcription factors involved in the mast cell lineage commitment. GMPs, which express C/EBP 𝛂 , turn on GATA-2 to become eosinophil progenitors (EoP). To form a progenitor with mast cell (MC) and basophil (Ba) potency, C/EBP 𝛂 is downregulated in the GMP along with upregulation of GATA2, GATA-3 and Hes-1. For MCp commitment, MITF is upregulated and C/EBP 𝛂 is further downregulated whereas for basophil progenitor (BaP) commitment MITF is downregulated and C/EBP 𝛂 is upregulated.CC-BY-NC-ND · From the PDF
Fig. 3 The major mechanisms involved in the increase of lung MCp during allergic inflammation. 1 , Committed MCp circulating in the blood express 𝛂 4-intergrins. 2 , Upon allergic inflammation in the lung VCAM-1 is induced on the lung endothelium enabling 𝛂 4-intergrin-expressing MCp to adhere to the lung endothelium and enter the tissue. 3 , MCp in the lung are influenced by locally produced factors that may stimulate them to divide in situ. 4 , Eventually most of the MCp will mature into long-lived mast cells. 5 , The increase in lung MCp numbers are strictly regulated by CD4 + T cells and CD11c + cells.
Fig. 3 The major mechanisms involved in the increase of lung MCp during allergic inflammation. 1 , Committed MCp circulating in the blood express 𝛂 4-intergrins. 2 , Upon allergic inflammation in the lung VCAM-1 is induced on the lung endothelium enabling 𝛂 4-intergrin-expressing MCp to adhere to the lung endothelium and enter the tissue. 3 , MCp in the lung are influenced by locally produced factors that may stimulate them to divide in situ. 4 , Eventually most of the MCp will mature into long-lived mast cells. 5 , The increase in lung MCp numbers are strictly regulated by CD4 + T cells and CD11c + cells.CC-BY-NC-ND · From the PDF
Fig. 4 The protocol used for investigating the mechanisms involved in MCp recruitment to lung during allergic inflammation. Mice were sensitized intraperitoneally (i.p.) days 0 and 7 with OVA in complex with alum. Starting ten days later (day 17), the mice were subjected to three daily treatments lasting for 30 min each with 1% OVA-aerosol. The quantification of MCp was done 24 h after the final challenge.
Fig. 4 The protocol used for investigating the mechanisms involved in MCp recruitment to lung during allergic inflammation. Mice were sensitized intraperitoneally (i.p.) days 0 and 7 with OVA in complex with alum. Starting ten days later (day 17), the mice were subjected to three daily treatments lasting for 30 min each with 1% OVA-aerosol. The quantification of MCp was done 24 h after the final challenge.CC-BY-NC-ND · From the PDF

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Authors
Dahlin, J. S., & Hallgren, J.
Venue
Molecular Immunology
Publisher
Elsevier BV
Published
2015-01
Volume
63
Issue
1
Pages
9-17
ISSN
0161-5890
DOI
10.1016/j.molimm.2014.01.018
Cited by
273
References
4
Language
en
Licence
Funders
  • Swedish Research Council
  • the Swedish Heart-Lung Foundation
  • Malin and Lennart Philipson Foundation
  • Bror Hjerpstedts Foundation
  • Agnes and Mac Rudberg Foundation
  • Lennander Foundation
  • Ellen, Walter and Lennart Hesselman Foundation

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