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Granulocyte Macrophage-Colony Stimulating Factor Produces a Splenic Subset of Monocyte-Derived Dendritic Cells That Efficiently Polarize T Helper Type 2 Cells in Response to Blood-Borne Antigen

 Seul Hye Ryu  ;  Hyun Soo Shin  ;  Hye Hyeon Eum  ;  Ji Soo Park  ;  Wanho Choi  ;  Hye Young Na  ;  Hyunju In  ;  Tae-Gyun Kim  ;  Sejung Park  ;  Soomin Hwang  ;  Moah Sohn  ;  Eun-Do Kim  ;  Kyoung Yul Seo  ;  Hae-Ock Lee  ;  Min-Geol Lee  ;  Min Kyung Chu  ;  Chae Gyu Park 
 FRONTIERS IN IMMUNOLOGY, Vol.12 : 767037, 2022-01 
Journal Title
Issue Date
Animals ; Antigen Presentation / immunology ; Antigens / immunology* ; Cell Differentiation / immunology ; Cells, Cultured ; Dendritic Cells / immunology* ; Granulocyte-Macrophage Colony-Stimulating Factor / immunology* ; Granulocytes / immunology* ; Macrophages / immunology* ; Membrane Proteins / immunology ; Mice ; Mice, Inbred C57BL ; Monocytes / immunology* ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / immunology ; Spleen / immunology* ; Th2 Cells / immunology*
GM-CSF ; GM-CSF receptor ; T cell – DC interactions ; Th2 cell ; allergic sensitization ; dendritic cell ; monocyte-derived dendritic cell ; spleen
Dendritic cells (DCs) are key antigen-presenting cells that prime naive T cells and initiate adaptive immunity. Although the genetic deficiency and transgenic overexpression of granulocyte macrophage-colony stimulating factor (GM-CSF) signaling were reported to influence the homeostasis of DCs, the in vivo development of DC subsets following injection of GM-CSF has not been analyzed in detail. Among the treatment of mice with different hematopoietic cytokines, only GM-CSF generates a distinct subset of XCR1-33D1- DCs which make up the majority of DCs in the spleen after three daily injections. These GM-CSF-induced DCs (GMiDCs) are distinguished from classical DCs (cDCs) in the spleen by their expression of CD115 and CD301b and by their superior ability to present blood-borne antigen and thus to stimulate CD4+ T cells. Unlike cDCs in the spleen, GMiDCs are exceptionally effective to polarize and expand T helper type 2 (Th2) cells and able to induce allergic sensitization in response to blood-borne antigen. Single-cell RNA sequencing analysis and adoptive cell transfer assay reveal the sequential differentiation of classical monocytes into pre-GMiDCs and GMiDCs. Interestingly, mixed bone marrow chimeric mice of Csf2rb +/+ and Csf2rb -/- demonstrate that the generation of GMiDCs necessitates the cis expression of GM-CSF receptor. Besides the spleen, GMiDCs are generated in the CCR7-independent resident DCs of the LNs and in some peripheral tissues with GM-CSF treatment. Also, small but significant numbers of GMiDCs are generated in the spleen and other tissues during chronic allergic inflammation. Collectively, our present study identifies a splenic subset of CD115hiCD301b+ GMiDCs that possess a strong capacity to promote Th2 polarization and allergic sensitization against blood-borne antigen.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Tae-Gyun(김태균) ORCID logo https://orcid.org/0000-0002-2116-4579
Park, Chae Gyu(박채규) ORCID logo https://orcid.org/0000-0003-1906-1308
Seo, Kyoung Yul(서경률) ORCID logo https://orcid.org/0000-0002-9855-1980
Chu, Min Kyung(주민경) ORCID logo https://orcid.org/0000-0001-6221-1346
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