PMID- 36069062
OWN - NLM
STAT- MEDLINE
DCOM- 20221003
LR  - 20230110
IS  - 1099-0844 (Electronic)
IS  - 0263-6484 (Print)
IS  - 0263-6484 (Linking)
VI  - 40
IP  - 7
DP  - 2022 Oct
TI  - Mouse dendritic cells in the steady state: Hypoxia, autophagy, and stem cell 
      factor.
PG  - 718-728
LID - 10.1002/cbf.3737 [doi]
AB  - Dendritic cells (DCs) are innate immune cells with a central role in immunity and 
      tolerance. Under steady-state, DCs are scattered in tissues as resting cells. 
      Upon infection or injury, DCs get activated and acquire the full capacity to 
      prime antigen-specific CD4(+) and CD8(+) T cells, thus bridging innate and 
      adaptive immunity. By secreting different sets of cytokines and chemokines, DCs 
      orchestrate diverse types of immune responses, from a classical proinflammatory 
      to an alternative pro-repair one. DCs are highly heterogeneous, and physiological 
      differences in tissue microenvironments greatly contribute to variations in DC 
      phenotype. Oxygen tension is normally low in some lymphoid areas, including bone 
      marrow (BM) hematopoietic niches; nevertheless, the possible impact of tissue 
      hypoxia on DC physiology has been poorly investigated. We assessed whether DCs 
      are hypoxic in BM and spleen, by staining for hypoxia-inducible-factor-1alpha subunit 
      (HIF-1alpha), the master regulator of hypoxia-induced response, and pimonidazole 
      (PIM), a hypoxic marker, and by flow cytometric analysis. Indeed, we observed 
      that mouse DCs have a hypoxic phenotype in spleen and BM, and showed some 
      remarkable differences between DC subsets. Notably, DCs expressing membrane 
      c-kit, the receptor for stem cell factor (SCF), had a higher PIM median 
      fluorescence intensity (MFI) than c-kit(-) DCs, both in the spleen and in the BM. 
      To determine whether SCF (a.k.a. kit ligand) has a role in DC hypoxia, we 
      evaluated molecular pathways activated by SCF in c-kit(+) BM-derived DCs cultured 
      in hypoxic conditions. Gene expression microarrays and gene set enrichment 
      analysis supported the hypothesis that SCF had an impact on hypoxia response and 
      inhibited autophagy-related gene sets. Our results suggest that hypoxic response 
      and autophagy, and their modulation by SCF, can play a role in DC homeostasis at 
      the steady state, in agreement with our previous findings on SCF's role in DC 
      survival.
CI  - (c) 2022 The Authors. Cell Biochemistry and Function published by John Wiley & Sons 
      Ltd.
FAU - Barroeta Seijas, Amairelys Belen
AU  - Barroeta Seijas AB
AUID- ORCID: 0000-0001-7538-4553
AD  - Institute of Molecular Biology and Pathology, National Research Council (CNR), 
      Rome, Italy.
FAU - Simonetti, Sonia
AU  - Simonetti S
AD  - Institute of Molecular Biology and Pathology, National Research Council (CNR), 
      Rome, Italy.
FAU - Filippi, Irene
AU  - Filippi I
AD  - Department of Molecular and Developmental Medicine, University of Siena, Siena, 
      Italy.
FAU - Naldini, Antonella
AU  - Naldini A
AD  - Department of Molecular and Developmental Medicine, University of Siena, Siena, 
      Italy.
FAU - Favaretto, Gabriele
AU  - Favaretto G
AD  - Institute of Molecular Biology and Pathology, National Research Council (CNR), 
      Rome, Italy.
FAU - Colombo, Teresa
AU  - Colombo T
AD  - Institute of Molecular Biology and Pathology, National Research Council (CNR), 
      Rome, Italy.
FAU - Natalini, Ambra
AU  - Natalini A
AD  - Institute of Molecular Biology and Pathology, National Research Council (CNR), 
      Rome, Italy.
FAU - Antonangeli, Fabrizio
AU  - Antonangeli F
AD  - Institute of Molecular Biology and Pathology, National Research Council (CNR), 
      Rome, Italy.
FAU - Laffranchi, Mattia
AU  - Laffranchi M
AUID- ORCID: 0000-0002-0556-6068
AD  - Department of Molecular Medicine, Sapienza University, Rome, Italy.
FAU - Sozzani, Silvano
AU  - Sozzani S
AD  - Department of Molecular Medicine, Sapienza University, Rome, Italy.
FAU - Santoni, Angela
AU  - Santoni A
AD  - Neuromed IRCCS, Pozzilli, Isernia, Italy.
AD  - Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Rome, Italy.
FAU - Di Rosa, Francesca
AU  - Di Rosa F
AUID- ORCID: 0000-0003-0252-9138
AD  - Institute of Molecular Biology and Pathology, National Research Council (CNR), 
      Rome, Italy.
LA  - eng
GR  - Associazione Italiana per la Ricerca sul Cancro/
GR  - Italian Minister of Research and University (MIUR) grant PRIN 2017K55HLC/
GR  - CNR Short Term Mobility (STM)/
PT  - Journal Article
DEP - 20220907
PL  - England
TA  - Cell Biochem Funct
JT  - Cell biochemistry and function
JID - 8305874
RN  - 0 (Cytokines)
RN  - 0 (Stem Cell Factor)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Autophagy
MH  - *CD8-Positive T-Lymphocytes
MH  - Cell Hypoxia
MH  - Cells, Cultured
MH  - Cytokines/metabolism
MH  - Dendritic Cells
MH  - Hypoxia/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oxygen/metabolism
MH  - *Stem Cell Factor/metabolism
PMC - PMC9826237
OTO - NOTNLM
OT  - bone marrow
OT  - c-kit
OT  - dendritic cells
OT  - hypoxia
OT  - stem cell factor
COIS- The authors declare no conflict of interest.
EDAT- 2022/09/08 06:00
MHDA- 2022/10/04 06:00
PMCR- 2023/01/08
CRDT- 2022/09/07 03:33
PHST- 2022/07/06 00:00 [revised]
PHST- 2022/04/25 00:00 [received]
PHST- 2022/08/09 00:00 [accepted]
PHST- 2022/09/08 06:00 [pubmed]
PHST- 2022/10/04 06:00 [medline]
PHST- 2022/09/07 03:33 [entrez]
PHST- 2023/01/08 00:00 [pmc-release]
AID - CBF3737 [pii]
AID - 10.1002/cbf.3737 [doi]
PST - ppublish
SO  - Cell Biochem Funct. 2022 Oct;40(7):718-728. doi: 10.1002/cbf.3737. Epub 2022 Sep 
      7.