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

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Cellular & Molecular Immunology 2023年第7期20卷 820-834页

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 Department of Biological Sciences Sungkyunkwan University2066 Seobu-roJangan-guSuwon-siGyeonggi-do 16419Republic of Korea Center for Immune Research on Non-Lymphoid Organs Sungkyunkwan University2066 Seobu-roJangan-guSuwon-siGyounggi-do 16419Republic of Korea Laboratory of Mucosal Immunology Department of Biomedical SciencesSeoul National University College of Medicine103 Daehak-roJongno-guSeoul 03080Republic of Korea Institute of Allergy and Clinical Immunology Seoul National University Medical Research CenterSeoulRepublic of Korea Department of Biochemistry College of Life Science and BiotechnologyYonsei UniversitySeoul 03722Republic of Korea Department of Nano Engineering and School of Chemical Engineering Sungkyunkwan University2066 Seobu-roJangan-guSuwon-siGyeonggi-do 16419Republic of Korea.

Recombinant interleukin-33(IL-33)inhibits tumor growth,but the detailed immunological mechanism is still ***-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 *** 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 *** 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 *** 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 *** GM-CSF also induced the population of CD103^(+)cDC1s,but the population neither expressed FCGR3 nor induced any discernable antitumor *** 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 ***-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 *** findings suggest that recombinant IL-33 or an IL-33-mediated DC vaccine could be an attractive protocol for better tumor immunotherapy.

关键词： Recombinant interleukin-33(IL-33) Highly immunogenic Spleen residency FCGR3^(+)CD103^(+)cDC1s ST2^(+)basophils Antitumor immunity

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