PMID- 32973804
OWN - NLM
STAT- MEDLINE
DCOM- 20210430
LR  - 20210430
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 11
DP  - 2020
TI  - Human Regulatory Dendritic Cells Develop From Monocytes in Response to Signals 
      From Regulatory and Helper T Cells.
PG  - 1982
LID - 10.3389/fimmu.2020.01982 [doi]
LID - 1982
AB  - Dendritic cells (DCs) are powerful antigen presenting cells, derived from bone 
      marrow progenitors (cDCs) and monocytes (moDCs), that can shape the immune 
      response by priming either proinflammatory or tolerogenic immune effector cells. 
      The cellular mechanisms responsible for the generation of DCs that will prime a 
      proinflammatory or tolerogenic response are poorly understood. Here we describe a 
      novel mechanism by which tolerogenic DCs are formed from monocytes. When human 
      monocytes were cultured with CD4(+)FoxP3(+) natural regulatory T cells (Tregs) 
      and T helper cells (Th) from healthy donor blood, they differentiated into 
      regulatory DCs (DC (Reg) ), capable of generating induced Tregs from naive T 
      cells. DC (Reg) exhibited morphology, surface phenotype, cytokine secretion, and 
      transcriptome that were distinct from other moDCs including those derived from 
      monocytes cultured with Th or with GM-CSF/IL-4, as well as macrophages (MPhi). 
      Direct cell contact between monocytes, Tregs and Th, along with Treg-derived 
      CTLA-4, IL-10 and TGF-beta, was required for the phenotypic differentiation of DC 
      (Reg) , although only IL-10 was required for imprinting the Treg-inducing 
      capacity of DC (Reg) . High ratios of Treg:Th, along with monocytes and DC (Reg) 
      similar in function and phenotype to those induced in vitro, were present in situ 
      in human colorectal cancer specimens. Thus, through the combined actions of Tregs 
      and Th, monocytes differentiate into DCs with regulatory properties, forming a 
      positive feedback loop to reinforce Treg initiated immune regulation. This 
      mechanism may contribute to immune tolerance in tissues such as tumors, which 
      contain an abundance of Tregs, Th and monocytes.
CI  - Copyright (c) 2020 Zhang, Zheng, Prestwood, Zhang, Carmi, Tolentino, Wu, Choi, 
      Winer, Strober, Kang, Alonso and Engleman.
FAU - Zhang, Xiangyue
AU  - Zhang X
AD  - Department of Pathology, Blood Center, Stanford University School of Medicine, 
      Palo Alto, CA, United States.
FAU - Zheng, Pingping
AU  - Zheng P
AD  - Bone Marrow Transplantation, Stanford University School of Medicine, Palo Alto, 
      CA, United States.
FAU - Prestwood, Tyler R
AU  - Prestwood TR
AD  - Department of Pathology, Blood Center, Stanford University School of Medicine, 
      Palo Alto, CA, United States.
FAU - Zhang, Hong
AU  - Zhang H
AD  - Department of Pathology, Blood Center, Stanford University School of Medicine, 
      Palo Alto, CA, United States.
FAU - Carmi, Yaron
AU  - Carmi Y
AD  - Department of Pathology, Blood Center, Stanford University School of Medicine, 
      Palo Alto, CA, United States.
FAU - Tolentino, Lorna L
AU  - Tolentino LL
AD  - Department of Pathology, Blood Center, Stanford University School of Medicine, 
      Palo Alto, CA, United States.
FAU - Wu, Nancy
AU  - Wu N
AD  - Department of Pathology, Blood Center, Stanford University School of Medicine, 
      Palo Alto, CA, United States.
FAU - Choi, Okmi
AU  - Choi O
AD  - Department of Pathology, Blood Center, Stanford University School of Medicine, 
      Palo Alto, CA, United States.
FAU - Winer, Daniel A
AU  - Winer DA
AD  - Buck Institute for Research on Aging, Novato, CA, United States.
AD  - Division of Cellular and Molecular Biology, Diabetes Research Group, Toronto 
      General Hospital Research Institute (TGHRI), University Health Network, Toronto, 
      ON, Canada.
FAU - Strober, Samuel
AU  - Strober S
AD  - Division of Immunology and Rheumatology, Department of Medicine, Stanford 
      University of Medicine, Stanford, CA, United States.
FAU - Kang, Eun-Suk
AU  - Kang ES
AD  - Department of Laboratory Medicine and Genetics, Samsung Medical Center, 
      Sungkyunkwan University, Seoul, South Korea.
FAU - Alonso, Michael N
AU  - Alonso MN
AD  - Department of Pathology, Blood Center, Stanford University School of Medicine, 
      Palo Alto, CA, United States.
FAU - Engleman, Edgar G
AU  - Engleman EG
AD  - Department of Pathology, Blood Center, Stanford University School of Medicine, 
      Palo Alto, CA, United States.
LA  - eng
GR  - P01 HL075462/HL/NHLBI NIH HHS/United States
GR  - R01 AI118884/AI/NIAID NIH HHS/United States
GR  - R01 CA222969/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20200818
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Biomarkers)
SB  - IM
MH  - Biomarkers
MH  - CD4-Positive T-Lymphocytes/immunology/metabolism
MH  - *Cell Communication/immunology
MH  - Cell Differentiation
MH  - Colonic Neoplasms/immunology/metabolism/pathology
MH  - Computational Biology/methods
MH  - Dendritic Cells/*immunology/*metabolism
MH  - Gene Expression Profiling
MH  - Humans
MH  - Immunomodulation
MH  - Immunophenotyping
MH  - Monocytes/*immunology/metabolism
MH  - *Signal Transduction
MH  - T-Lymphocyte Subsets/immunology/metabolism
MH  - T-Lymphocytes, Regulatory/*immunology/*metabolism
MH  - Transcriptome
PMC - PMC7461788
OTO - NOTNLM
OT  - DCReg
OT  - DCs
OT  - Th
OT  - Tregs
OT  - monocytes
EDAT- 2020/09/26 06:00
MHDA- 2021/05/01 06:00
PMCR- 2020/01/01
CRDT- 2020/09/25 06:02
PHST- 2020/04/08 00:00 [received]
PHST- 2020/07/22 00:00 [accepted]
PHST- 2020/09/25 06:02 [entrez]
PHST- 2020/09/26 06:00 [pubmed]
PHST- 2021/05/01 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2020.01982 [doi]
PST - epublish
SO  - Front Immunol. 2020 Aug 18;11:1982. doi: 10.3389/fimmu.2020.01982. eCollection 
      2020.