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.
|Journal||Frontiers in Immunology|
|Publication status||Published - 2022 Jan 3|
Bibliographical noteFunding Information:
We thank the Department of Laboratory Animal Resources, the Flow Cytometry Core Facility, the Yonsei Advanced Imaging Center in cooperation with Carl Zeiss Microscopy, and the Medical Illustration & Design (MID) of the Yonsei University College of Medicine for their kind help and technical support; Ho-Keun Kwon and Kichun Kim for help with experiments; Niroshana Anandasabapathy and Uri Sela for critical comments on the manuscript; JW CreaGene for their generous gift of cytokine samples.
Copyright © 2022 Ryu, Shin, Eum, Park, Choi, Na, In, Kim, Park, Hwang, Sohn, Kim, Seo, Lee, Lee, Chu and Park.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy