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

• Published in: Frontiers in immunology 2022-01, Vol.12, p.767037-767037
• Main Authors: Ryu, Seul Hye, Shin, Hyun Soo, Eum, Hye Hyeon, Park, Ji Soo, Choi, Wanho, Na, Hye Young, In, Hyunju, Kim, Tae-Gyun, Park, Sejung, Hwang, Soomin, Sohn, Moah, Kim, Eun-Do, Seo, Kyoung Yul, Lee, Hae-Ock, Lee, Min-Geol, Chu, Min Kyung, Park, Chae Gyu
• Format: Article
• Language: English
• Subjects: allergic sensitization; Animals; Antigen Presentation - immunology; Antigens - immunology; Cell Differentiation - immunology; Cells, Cultured; dendritic cell; Dendritic Cells - immunology; GM-CSF; GM-CSF receptor; Granulocyte-Macrophage Colony-Stimulating Factor - immunology; Granulocytes - immunology; Immunology; Macrophages - immunology; Membrane Proteins - immunology; Mice; Mice, Inbred C57BL; monocyte-derived dendritic cell; Monocytes - immunology; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor - immunology; spleen; Spleen - immunology; Th2 Cells - immunology
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.767037

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 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 and demonstrate that the generation of GMiDCs necessitates the 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 CD115 CD301b GMiDCs that possess a strong capacity to promote Th2 polarization and allergic sensitization against blood-borne antigen.