PMID- 38416039
OWN - NLM
STAT- MEDLINE
DCOM- 20240403
LR  - 20240430
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 212
IP  - 8
DP  - 2024 Apr 15
TI  - Single-Cell Analysis Reveals a Subset of High IL-12p40-Secreting Dendritic Cells 
      within Mouse Bone Marrow-Derived Macrophages Differentiated with M-CSF.
PG  - 1357-1365
LID - 10.4049/jimmunol.2300431 [doi]
AB  - Macrophages and dendritic cells (DCs), although ontogenetically distinct, have 
      overlapping functions and exhibit substantial cell-to-cell heterogeneity that can 
      complicate their identification and obscure innate immune function. In this 
      study, we report that M-CSF-differentiated murine bone marrow-derived macrophages 
      (BMDMs) exhibit extreme heterogeneity in the production of IL-12, a key 
      proinflammatory cytokine linking innate and adaptive immunity. A microwell 
      secretion assay revealed that a small fraction of BMDMs stimulated with LPS 
      secrete most IL-12p40, and we confirmed that this is due to extremely high 
      expression of Il12b, the gene encoding IL-12p40, in a subset of cells. Using an 
      Il12b-YFP reporter mouse, we isolated cells with high LPS-induced Il12b 
      expression and found that this subset was enriched for genes associated with the 
      DC lineage. Single-cell RNA sequencing data confirmed a DC-like subset that 
      differentiates within BMDM cultures that is transcriptionally distinct but could 
      not be isolated by surface marker expression. Although not readily apparent in 
      the resting state, upon LPS stimulation, this subset exhibited a typical 
      DC-associated activation program that is distinct from LPS-induced stochastic 
      BMDM cell-to-cell heterogeneity. Overall, our findings underscore the difficulty 
      in distinguishing macrophages and DCs even in widely used in vitro murine BMDM 
      cultures and could affect the interpretation of some studies that use BMDMs to 
      explore acute inflammatory responses.
CI  - Copyright (c) 2024 by The American Association of Immunologists, Inc.
FAU - Bridges, Kate
AU  - Bridges K
AUID- ORCID: 0000-0003-3642-7068
AD  - Department of Biomedical Engineering, Yale University, New Haven, CT.
FAU - Pizzurro, Gabriela A
AU  - Pizzurro GA
AUID- ORCID: 0000-0002-1193-9385
AD  - Department of Biomedical Engineering, Yale University, New Haven, CT.
FAU - Khunte, Mihir
AU  - Khunte M
AUID- ORCID: 0000-0003-2995-3203
AD  - Department of Biomedical Engineering, Yale University, New Haven, CT.
FAU - Chen, Meibin
AU  - Chen M
AUID- ORCID: 0000-0001-9754-7421
AD  - Department of Biomedical Engineering, Yale University, New Haven, CT.
FAU - Salvador Rocha, Erick
AU  - Salvador Rocha E
AD  - Department of Microbiology, Yale University, New Haven, CT.
FAU - Alexander, Amanda F
AU  - Alexander AF
AUID- ORCID: 0000-0002-6690-8244
AD  - Department of Biomedical Engineering, Yale University, New Haven, CT.
FAU - Bass, Victor
AU  - Bass V
AD  - Department of Molecular, Cellular, and Developmental Biology, Yale University, 
      New Haven, CT.
FAU - Kellman, Laura N
AU  - Kellman LN
AUID- ORCID: 0000-0002-1073-8936
AD  - Department of Molecular, Cellular, and Developmental Biology, Yale University, 
      New Haven, CT.
FAU - Baskaran, Janani
AU  - Baskaran J
AUID- ORCID: 0000-0002-4764-9611
AD  - Department of Biomedical Engineering, Yale University, New Haven, CT.
FAU - Miller-Jensen, Kathryn
AU  - Miller-Jensen K
AD  - Department of Biomedical Engineering, Yale University, New Haven, CT.
AD  - Department of Molecular, Cellular, and Developmental Biology, Yale University, 
      New Haven, CT.
LA  - eng
GR  - R01 GM123011/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
RN  - 0 (Interleukin-12 Subunit p40)
RN  - 0 (Lipopolysaccharides)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Macrophage Colony-Stimulating Factor/metabolism
MH  - *Interleukin-12 Subunit p40/genetics/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages
MH  - Dendritic Cells
MH  - Single-Cell Analysis
EDAT- 2024/02/28 12:42
MHDA- 2024/04/03 06:44
CRDT- 2024/02/28 10:01
PHST- 2023/07/07 00:00 [received]
PHST- 2024/02/01 00:00 [accepted]
PHST- 2024/04/03 06:44 [medline]
PHST- 2024/02/28 12:42 [pubmed]
PHST- 2024/02/28 10:01 [entrez]
AID - 266727 [pii]
AID - 10.4049/jimmunol.2300431 [doi]
PST - ppublish
SO  - J Immunol. 2024 Apr 15;212(8):1357-1365. doi: 10.4049/jimmunol.2300431.