PMID- 35069539 OWN - NLM STAT- MEDLINE DCOM- 20220221 LR - 20220221 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 12 DP - 2021 TI - 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. PG - 767037 LID - 10.3389/fimmu.2021.767037 [doi] LID - 767037 AB - 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 CD115(hi)CD301b(+) GMiDCs that possess a strong capacity to promote Th2 polarization and allergic sensitization against blood-borne antigen. CI - Copyright (c) 2022 Ryu, Shin, Eum, Park, Choi, Na, In, Kim, Park, Hwang, Sohn, Kim, Seo, Lee, Lee, Chu and Park. FAU - Ryu, Seul Hye AU - Ryu SH AD - Laboratory of Immunology, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea. AD - Brain Korea 21 FOUR Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. AD - Immune and Vascular Cell Network Research Center, National Creative Initiatives, Department of Life Sciences, Ewha Womans University, Seoul, South Korea. FAU - Shin, Hyun Soo AU - Shin HS AD - Laboratory of Immunology, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea. AD - Brain Korea 21 FOUR Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. FAU - Eum, Hye Hyeon AU - Eum HH AD - Department of Biomedicine and Health Sciences, Graduate School, The Catholic University of Korea, Seoul, South Korea. AD - Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, South Korea. FAU - Park, Ji Soo AU - Park JS AD - Laboratory of Immunology, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea. AD - Brain Korea 21 FOUR Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. FAU - Choi, Wanho AU - Choi W AD - Laboratory of Immunology, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea. AD - Brain Korea 21 FOUR Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. FAU - Na, Hye Young AU - Na HY AD - Laboratory of Immunology, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea. AD - Department of Neurology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. FAU - In, Hyunju AU - In H AD - Laboratory of Immunology, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea. AD - Brain Korea 21 FOUR Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. FAU - Kim, Tae-Gyun AU - Kim TG AD - Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, South Korea. FAU - Park, Sejung AU - Park S AD - Laboratory of Immunology, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea. AD - Brain Korea 21 FOUR Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. FAU - Hwang, Soomin AU - Hwang S AD - Laboratory of Immunology, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea. AD - Brain Korea 21 FOUR Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. FAU - Sohn, Moah AU - Sohn M AD - Laboratory of Immunology, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea. AD - Brain Korea 21 FOUR Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. FAU - Kim, Eun-Do AU - Kim ED AD - Department of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, Seoul, South Korea. FAU - Seo, Kyoung Yul AU - Seo KY AD - Department of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, Seoul, South Korea. FAU - Lee, Hae-Ock AU - Lee HO AD - Department of Biomedicine and Health Sciences, Graduate School, The Catholic University of Korea, Seoul, South Korea. AD - Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, South Korea. FAU - Lee, Min-Geol AU - Lee MG AD - Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, South Korea. FAU - Chu, Min Kyung AU - Chu MK AD - Department of Neurology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. FAU - Park, Chae Gyu AU - Park CG AD - Laboratory of Immunology, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea. AD - Therapeutic Antibody Research Center, Genuv Inc., Seoul, South Korea. AD - Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220103 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Antigens) RN - 0 (Membrane Proteins) RN - 0 (Receptors, Granulocyte-Macrophage Colony-Stimulating Factor) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - Animals MH - Antigen Presentation/immunology MH - Antigens/*immunology MH - Cell Differentiation/immunology MH - Cells, Cultured MH - Dendritic Cells/*immunology MH - Granulocyte-Macrophage Colony-Stimulating Factor/*immunology MH - Granulocytes/*immunology MH - Macrophages/*immunology MH - Membrane Proteins/immunology MH - Mice MH - Mice, Inbred C57BL MH - Monocytes/*immunology MH - Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/immunology MH - Spleen/*immunology MH - Th2 Cells/*immunology PMC - PMC8778578 OTO - NOTNLM OT - GM-CSF OT - GM-CSF receptor OT - T cell - DC interactions OT - Th2 cell OT - allergic sensitization OT - dendritic cell OT - monocyte-derived dendritic cell OT - spleen COIS- Author CP is employed by Genuv Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/01/25 06:00 MHDA- 2022/02/22 06:00 PMCR- 2021/01/01 CRDT- 2022/01/24 08:49 PHST- 2021/08/30 00:00 [received] PHST- 2021/12/06 00:00 [accepted] PHST- 2022/01/24 08:49 [entrez] PHST- 2022/01/25 06:00 [pubmed] PHST- 2022/02/22 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2021.767037 [doi] PST - epublish SO - Front Immunol. 2022 Jan 3;12:767037. doi: 10.3389/fimmu.2021.767037. eCollection 2021.