PMID- 32610077 OWN - NLM STAT- MEDLINE DCOM- 20210413 LR - 20240210 IS - 1097-4180 (Electronic) IS - 1074-7613 (Print) IS - 1074-7613 (Linking) VI - 53 IP - 2 DP - 2020 Aug 18 TI - Transcriptional and Functional Analysis of CD1c(+) Human Dendritic Cells Identifies a CD163(+) Subset Priming CD8(+)CD103(+) T Cells. PG - 335-352.e8 LID - S1074-7613(20)30232-6 [pii] LID - 10.1016/j.immuni.2020.06.002 [doi] AB - Dendritic cells (DCs) are antigen-presenting cells controlling T cell activation. In humans, the diversity, ontogeny, and functional capabilities of DC subsets are not fully understood. Here, we identified circulating CD88(-)CD1c(+)CD163(+) DCs (called DC3s) as immediate precursors of inflammatory CD88(-)CD14(+)CD1c(+)CD163(+)FcepsilonRI(+) DCs. DC3s develop via a specific pathway activated by GM-CSF, independent of cDC-restricted (CDP) and monocyte-restricted (cMoP) progenitors. Like classical DCs but unlike monocytes, DC3s drove activation of naive T cells. In vitro, DC3s displayed a distinctive ability to prime CD8(+) T cells expressing a tissue homing signature and the epithelial homing alpha-E integrin (CD103) through transforming growth factor beta (TGF-beta) signaling. In vivo, DC3s infiltrated luminal breast cancer primary tumors, and DC3 infiltration correlated positively with CD8(+)CD103(+)CD69(+) tissue-resident memory T cells. Together, these findings define DC3s as a lineage of inflammatory DCs endowed with a strong potential to regulate tumor immunity. CI - Copyright (c) 2020 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Bourdely, Pierre AU - Bourdely P AD - Centre for Inflammation Biology and Cancer Immunology, The Peter Gorer Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, London, UK; Cancer Research UK King's Health Partner Cancer Centre, King's College London, London, UK. FAU - Anselmi, Giorgio AU - Anselmi G AD - Centre for Inflammation Biology and Cancer Immunology, The Peter Gorer Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, London, UK; Cancer Research UK King's Health Partner Cancer Centre, King's College London, London, UK. FAU - Vaivode, Kristine AU - Vaivode K AD - Centre for Inflammation Biology and Cancer Immunology, The Peter Gorer Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, London, UK; Cancer Research UK King's Health Partner Cancer Centre, King's College London, London, UK. FAU - Ramos, Rodrigo Nalio AU - Ramos RN AD - PSL Research University, Institut Curie Research Center, Translational Immunotherapy Team, INSERM U932, Paris, France. FAU - Missolo-Koussou, Yoann AU - Missolo-Koussou Y AD - PSL Research University, Institut Curie Research Center, Translational Immunotherapy Team, INSERM U932, Paris, France. FAU - Hidalgo, Sofia AU - Hidalgo S AD - PSL Research University, Institut Curie Research Center, Translational Immunotherapy Team, INSERM U932, Paris, France; Laboratory of Immuno-oncology, Fundacion Ciencia & Vida, Santiago, Chile. FAU - Tosselo, Jimena AU - Tosselo J AD - PSL Research University, Institut Curie Research Center, Translational Immunotherapy Team, INSERM U932, Paris, France. FAU - Nunez, Nicolas AU - Nunez N AD - PSL Research University, Institut Curie Research Center, Translational Immunotherapy Team, INSERM U932, Paris, France. FAU - Richer, Wilfrid AU - Richer W AD - PSL Research University, Institut Curie Research Center, Translational Immunotherapy Team, INSERM U932, Paris, France. FAU - Vincent-Salomon, Anne AU - Vincent-Salomon A AD - PSL Research University, Institut Curie, Department of Biopathology, Paris, France. FAU - Saxena, Alka AU - Saxena A AD - National Institute of Health Research Biomedical Research Centre at Guy's and St Thomas' Hospital and King's College London, London, UK. FAU - Wood, Kristie AU - Wood K AD - National Institute of Health Research Biomedical Research Centre at Guy's and St Thomas' Hospital and King's College London, London, UK. FAU - Lladser, Alvaro AU - Lladser A AD - Laboratory of Immuno-oncology, Fundacion Ciencia & Vida, Santiago, Chile; Facultad de Medicina y Ciencia, Universidad San Sebastian, Santiago, Chile. FAU - Piaggio, Eliane AU - Piaggio E AD - PSL Research University, Institut Curie Research Center, Translational Immunotherapy Team, INSERM U932, Paris, France. FAU - Helft, Julie AU - Helft J AD - PSL Research University, Institut Curie Research Center, Translational Immunotherapy Team, INSERM U932, Paris, France. FAU - Guermonprez, Pierre AU - Guermonprez P AD - Centre for Inflammation Biology and Cancer Immunology, The Peter Gorer Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, London, UK; Cancer Research UK King's Health Partner Cancer Centre, King's College London, London, UK; Universite de Paris, Centre for Inflammation Research, CNRS ERL8252, INSERM1149 Paris, France. Electronic address: pierre.guermonprez@kcl.ac.uk. LA - eng GR - 22369/CRUK_/Cancer Research UK/United Kingdom GR - NC/K001868/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom GR - DH_/Department of Health/United Kingdom GR - BB_/Biotechnology and Biological Sciences Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200630 PL - United States TA - Immunity JT - Immunity JID - 9432918 RN - 0 (Antigens, CD) RN - 0 (Antigens, CD1) RN - 0 (Antigens, Differentiation, Myelomonocytic) RN - 0 (CD163 antigen) RN - 0 (CD1C protein, human) RN - 0 (CD8 Antigens) RN - 0 (CSF2 protein, human) RN - 0 (Glycoproteins) RN - 0 (Integrin alpha Chains) RN - 0 (Receptors, Cell Surface) RN - 0 (TGFB1 protein, human) RN - 0 (Transforming Growth Factor beta1) RN - 0 (alpha E integrins) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) RN - EC 2.7.10.1 (FLT3 protein, human) RN - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3) SB - IM CIN - Immunity. 2020 Aug 18;53(2):233-235. PMID: 32814019 MH - Animals MH - Antigens, CD/*metabolism MH - Antigens, CD1/*metabolism MH - Antigens, Differentiation, Myelomonocytic/*metabolism MH - Breast Neoplasms/*immunology MH - CD8 Antigens/metabolism MH - CD8-Positive T-Lymphocytes/*cytology/immunology MH - Cell Differentiation/immunology MH - Cell Line, Tumor MH - Dendritic Cells/*immunology MH - Glycoproteins/*metabolism MH - Granulocyte-Macrophage Colony-Stimulating Factor/metabolism MH - Humans MH - Integrin alpha Chains/*metabolism MH - Lymphocyte Activation/immunology MH - Mice MH - Mice, Inbred NOD MH - Receptors, Cell Surface/*metabolism MH - Transforming Growth Factor beta1/metabolism MH - fms-Like Tyrosine Kinase 3/metabolism PMC - PMC7445430 OTO - NOTNLM OT - DC progenitors OT - DC3s OT - T(RM) OT - cDC2s OT - conventional DCs OT - inflammatory DCs OT - monocytes OT - mononuclear phagocytes COIS- Declaration of Interests The authors declare no competing interests. EDAT- 2020/07/02 06:00 MHDA- 2021/04/14 06:00 PMCR- 2020/08/18 CRDT- 2020/07/02 06:00 PHST- 2019/05/18 00:00 [received] PHST- 2020/04/15 00:00 [revised] PHST- 2020/05/29 00:00 [accepted] PHST- 2020/07/02 06:00 [pubmed] PHST- 2021/04/14 06:00 [medline] PHST- 2020/07/02 06:00 [entrez] PHST- 2020/08/18 00:00 [pmc-release] AID - S1074-7613(20)30232-6 [pii] AID - 10.1016/j.immuni.2020.06.002 [doi] PST - ppublish SO - Immunity. 2020 Aug 18;53(2):335-352.e8. doi: 10.1016/j.immuni.2020.06.002. Epub 2020 Jun 30.