气候变化领域集成服务门户(CCPortal): Altered ratio of dendritic cell subsets in skin-draining lymph nodes promotes Th2-driven contact hypersensitivity

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DOI	10.1073/pnas.2021364118
	Altered ratio of dendritic cell subsets in skin-draining lymph nodes promotes Th2-driven contact hypersensitivity
	Miller H.L.; Andhey P.S.; Swiecki M.K.; Rosa B.A.; Zaitsev K.; Villani A.-C.; Mitreva M.; Artyomov M.N.; Gilfillan S.; Cella M.; Colonna M.
发表日期	2021
ISSN	00278424
卷号	118 期号:3
英文摘要	Plasmacytoid dendritic cells (pDCs) specialize in the production of type I IFN (IFN-I). pDCs can be depleted in vivo by injecting diphtheria toxin (DT) in a mouse in which pDCs express a diphtheria toxin receptor (DTR) transgene driven by the human CLEC4C promoter. This promoter is enriched for binding sites for TCF4, a transcription factor that promotes pDC differentiation and expression of pDC markers, including CLEC4C. Here, we found that injection of DT in CLEC4C-DTR+ mice markedly augmented Th2-dependent skin inflammation in a model of contact hypersensitivity (CHS) induced by the hapten fluorescein isothiocyanate. Unexpectedly, this biased Th2 response was independent of reduced IFN-I accompanying pDC depletion. In fact, DT treatment altered the representation of conventional dendritic cells (cDCs) in the skin-draining lymph nodes during the sensitization phase of CHS; there were fewer Th1-priming CD326+ CD103+ cDC1 and more Th2-priming CD11b+ cDC2. Single-cell RNA-sequencing of CLEC4C-DTR+ cDCs revealed that CD326+ DCs, like pDCs, expressed DTR and were depleted together with pDCs by DT treatment. Since CD326+ DCs did not express Tcf4, DTR expression might be driven by yet-undefined transcription factors activating the CLEC4C promoter. These results demonstrate that altered DC representation in the skin-draining lymph nodes during sensitization to allergens can cause Th2-driven CHS. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Allergy; Contact hypersensitivity; Plasmacytoid DC; Skin; Th2
语种	英语
scopus关键词	CD103 antigen; CD11b antigen; diphtheria toxin; epithelial cell adhesion molecule; fluorescein isothiocyanate; gamma interferon; hapten; interferon; receptor; transcription factor 4; animal cell; animal experiment; animal model; Article; CD4+ T lymphocyte; CLEC4C gene; contact allergy; controlled study; dermatitis; disease exacerbation; gene; lymph node; mouse; nonhuman; plasmacytoid dendritic cell; priority journal; protein expression; single cell RNA seq; skin sensitization; Th1 cell; Th2 cell; transgenic mouse
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180937
作者单位	Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, United States; Discovery Immunology, Janssen Research & Development, Spring House, PA 19477, United States; Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States; McDonnell Genome Institute, Washington University, St. Louis, MO 63110, United States; Computer Technologies Department, ITMO University, St. Petersburg, 197101, Russian Federation; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02114, United States
推荐引用方式 GB/T 7714	Miller H.L.,Andhey P.S.,Swiecki M.K.,et al. Altered ratio of dendritic cell subsets in skin-draining lymph nodes promotes Th2-driven contact hypersensitivity[J],2021,118(3).
APA	Miller H.L..,Andhey P.S..,Swiecki M.K..,Rosa B.A..,Zaitsev K..,...&Colonna M..(2021).Altered ratio of dendritic cell subsets in skin-draining lymph nodes promotes Th2-driven contact hypersensitivity.Proceedings of the National Academy of Sciences of the United States of America,118(3).
MLA	Miller H.L.,et al."Altered ratio of dendritic cell subsets in skin-draining lymph nodes promotes Th2-driven contact hypersensitivity".Proceedings of the National Academy of Sciences of the United States of America 118.3(2021).