Discovery of highly immunogenic spleen-resident FCGR3+CD103+ cDC1s differentiated by IL-33-primed ST2+ basophils

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外文摘要：Recombinant interleukin-33(IL-33)inhibits tumor growth,but the detailed immunological mechanism is still unknown.IL-33-mediated tumor suppression did not occur in Batf3-/-mice,indicating that conventional type 1 dendritic cells(cDC1s)play a key role in IL-33-mediated antitumor immunity.A population of CD103+ cDC1s,which were barely detectable in the spleens of normal mice,increased significantly in the spleens of IL-33-treated mice.The newly emerged splenic CD103+ cDC1s were distinct from conventional splenic cDC1s based on their spleen residency,robust effector T-cell priming ability,and surface expression of FCGR3.DCs and DC precursors did not express Suppressor of Tumorigenicity 2(ST2).However,recombinant IL-33 induced spleen-resident FCGR3+CD103+ cDC1s,which were found to be differentiated from DC precursors by bystander ST2+ immune cells.Through immune cell fractionation and depletion assays,we found that IL-33-primed ST2+ basophils play a crucial role in the development of FCGR3+CD103+ cDC1s by secreting IL-33-driven extrinsic factors.Recombinant GM-CSF also induced the population of CD103+ cDC1s,but the population neither expressed FCGR3 nor induced any discernable antitumor immunity.The population of FCGR3+CD103+ cDC1s was also generated in vitro culture of Flt3L-mediated bone marrow-derived DCs(FL-BMDCs)when IL-33 was added in a pre-DC stage of culture.FL-BMDCs generated in the presence of IL-33(FL-33-DCs)offered more potent tumor immunotherapy than control Flt3L-BMDCs(FL-DCs).Human monocyte-derived DCs were also more immunogenic when exposed to IL-33-induced factors.Our findings suggest that recombinant IL-33 or an IL-33-mediated DC vaccine could be an attractive protocol for better tumor immunotherapy.

外文关键词：

Recombinant interleukin-33(IL-33)Highly immunogenicSpleen residencyFCGR3+CD103+ cDC1sST2+ basophilsAntitumor immunity

作者：

Myeong-Ho Kang、JungHyub Hong、Jinjoo Lee、Min-Suk Cha、Sangho Lee、Hye-Young Kim、Sang-Jun Ha、Yong Taik Lim、Yong-Soo Bae

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作者单位：

Department of Biological Sciences,Sungkyunkwan University,2066 Seobu-ro,Jangan-gu,Suwon-si,Gyeonggi-do 16419,Republic of Korea

Center for Immune Research on Non-Lymphoid Organs,Sungkyunkwan University,2066 Seobu-ro,Jangan-gu,Suwon-si,Gyounggi-do 16419,Republic of Korea

Laboratory of Mucosal Immunology,Department of Biomedical Sciences,Seoul National University College of Medicine,103 Daehak-ro,Jongno-gu,Seoul 03080,Republic of Korea

Institute of Allergy and Clinical Immunology,Seoul National University Medical Research Center,Seoul,Republic of Korea

Department of Biochemistry,College of Life Science and Biotechnology,Yonsei University,Seoul 03722,Republic of Korea

Department of Nano Engineering and School of Chemical Engineering,Sungkyunkwan University,2066 Seobu-ro,Jangan-gu,Suwon-si,Gyeonggi-do 16419,Republic of Korea

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基金：

National Research Foundation of Korea

项目编号：

SRC-2017R1A5A1014560

出版年：

2023

DOI：

10.1038/s41423-023-01035-8

中国免疫学杂志(英文版)

中国免疫学会

中国免疫学杂志(英文版)

CSTPCDCSCDSCI

影响因子：0.731

ISSN：1672-7681

年,卷(期)：2023.20(7)

参考文献量75