title: Human Blood CD1c+ Dendritic Cells Encompass CD5high and CD5low Subsets That Differ Significantly in Phenotype, Gene Expression, and Functions.
abstract: There are three major dendritic cell (DC) subsets in both humans and mice, that is, plasmacytoid DCs and two types of conventional DCs (cDCs), cDC1s and cDC2s. cDC2s are important for polarizing CD4+naive T cells into different subsets, including Th1, Th2, Th17, Th22, and regulatory T cells. In mice, cDC2s can be further divided into phenotypically and functionally distinct subgroups. However, subsets of human cDC2s have not been reported. In the present study, we showed that human blood CD1c+cDCs (cDC2s) can be further separated into two subpopulations according to their CD5 expression status. Comparative transcriptome analyses showed that the CD5highDCs expressed higher levels of cDC2-specific genes, including IFN regulatory factor 4, which is essential for the cDC2 development and its migration to lymph nodes. In contrast, CD5lowDCs preferentially expressed monocyte-related genes, including the lineage-specific transcription factor MAFB. Furthermore, compared with the CD5lowsubpopulation, the CD5highsubpopulation showed stronger migration toward CCL21 and overrepresentation among migratory DCs in lymph nodes. Additionally, the CD5highDCs induced naive T cell proliferation more potently than did the CD5lowDCs. Moreover, CD5highDCs induced higher levels of IL-10-, IL-22-, and IL-4-producing T cell formation, whereas CD5lowDCs induced higher levels of IFN-γ-producing T cell formation. Thus, we show that human blood CD1c+cDC2s encompass two subsets that differ significantly in phenotype, that is, gene expression and functions. We propose that these two subsets of human cDC2s could potentially play contrasting roles in immunity or tolerance.
authors.affiliation: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.|University of Chinese Academy of Sciences, Beijing 100080, China.
authors.forename: Xiangyun
authors.identifier: 0000-0003-0903-2319
authors.initials: X
authors.lastname: Yin
authors.affiliation: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.|University of Chinese Academy of Sciences, Beijing 100080, China.
authors.forename: Haisheng
authors.initials: H
authors.lastname: Yu
authors.affiliation: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.|University of Chinese Academy of Sciences, Beijing 100080, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Jin
authors.affiliation: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jingyun
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Cardiology, 306th Hospital of Chinese People's Liberation Army, Beijing 100101, China; and.
authors.forename: Quanxing
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Department of Cardiology, 306th Hospital of Chinese People's Liberation Army, Beijing 100101, China; and.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Cardiology, 306th Hospital of Chinese People's Liberation Army, Beijing 100101, China; and.
authors.forename: Shouli
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; liguozhang@ibp.ac.cn.
authors.forename: Liguo
authors.initials: L
authors.lastname: Zhang
mesh_terms: D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology*; D001773:Blood Cells / Q000276:immunology; D018956:CD5 Antigens / Q000032:analysis / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects; D054421:Chemokine CCL21 / Q000494:pharmacology; D003713:Dendritic Cells / Q000145:classification / Q000187:drug effects / Q000276:immunology* / Q000502:physiology*; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation; D010641:Phenotype; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D000097043:Interleukin-22; D000099218:Interferon Regulatory Factor-4
chemical_list: D018949:Antigens, CD1; D018956:CD5 Antigens; D054421:Chemokine CCL21; D006023:Glycoproteins; D050835:Interferon Regulatory Factors; D016753:Interleukin-10; D015847:Interleukin-4; D007378:Interleukins; D000097043:Interleukin-22; D000099218:Interferon Regulatory Factor-4; C515478:CCL21 protein, human; C437944:CD1C protein, human; C508609:IL10 protein, human