PMID- 37958886
OWN - NLM
STAT- MEDLINE
DCOM- 20231115
LR  - 20231117
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 21
DP  - 2023 Nov 2
TI  - The Tolerogenic Influence of Dexamethasone on Dendritic Cells Is Accompanied by 
      the Induction of Efferocytosis, Promoted by MERTK.
LID - 10.3390/ijms242115903 [doi]
LID - 15903
AB  - Many treatments for autoimmune diseases, caused by the loss of immune 
      self-tolerance, are broadly immunosuppressive. Dendritic cells (DCs) can be 
      induced to develop anti-inflammatory/tolerogenic properties to suppress aberrant 
      self-directed immunity by promoting immune tolerance in an antigen-specific 
      manner. Dexamethasone can generate tolerogenic DCs and upregulates MERTK 
      expression. As MERTK can inhibit inflammation, we investigated whether 
      dexamethasone's tolerogenic effects are mediated via MERTK, potentially providing 
      a novel therapeutic approach. Monocyte-derived DCs were treated with 
      dexamethasone, and with and without MERTK ligands or MERTK inhibitors. Flow 
      cytometry was used to assess effects of MERTK modulation on co-stimulatory 
      molecule expression, efferocytosis, cytokine secretion and T cell proliferation. 
      The influence on expression of Rab17, which coordinates the diversion of 
      efferocytosed material away from cell surface presentation, was assessed. 
      Dexamethasone-treated DCs had upregulated MERTK expression, decreased expression 
      of co-stimulatory molecules, maturation and proliferation of co-cultured T cells 
      and increased uptake of myelin debris. MERTK ligands did not potentiate these 
      properties, whilst specific MERTK inhibition only reversed dexamethasone's effect 
      on myelin uptake. Cells undergoing efferocytosis had higher Rab17 expression. 
      Dexamethasone-enhanced efferocytosis in DCs is MERTK-dependent and could exert 
      its tolerogenic effects by increasing Rab17 expression to prevent the 
      presentation of efferocytosed material on the cell surface to activate adaptive 
      immune responses.
FAU - Li, Vivien
AU  - Li V
AUID- ORCID: 0000-0001-9889-971X
AD  - The Florey Institute of Neuroscience and Mental Health, University of Melbourne, 
      Parkville, VIC 3010, Australia.
FAU - Binder, Michele D
AU  - Binder MD
AD  - The Florey Institute of Neuroscience and Mental Health, University of Melbourne, 
      Parkville, VIC 3010, Australia.
AD  - Department of Anatomy and Physiology, University of Melbourne, Parkville, VIC 
      3010, Australia.
FAU - Kilpatrick, Trevor J
AU  - Kilpatrick TJ
AD  - The Florey Institute of Neuroscience and Mental Health, University of Melbourne, 
      Parkville, VIC 3010, Australia.
LA  - eng
GR  - GNT1191292/National Health and Medical Research Council/
GR  - Education and Research Foundation/Australian and New Zealand Association of 
      Neurologists/
GR  - 19-0720/Multiple Sclerosis Research Australia/
GR  - 19-0720/Trish Multiple Sclerosis Research Foundation/
GR  - N/A/Australian Rotary Health/
GR  - APP1175775/National Health and Medical Research Council/
PT  - Journal Article
DEP - 20231102
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - EC 2.7.10.1 (c-Mer Tyrosine Kinase)
RN  - 0 (Immunosuppressive Agents)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - c-Mer Tyrosine Kinase/genetics/metabolism
MH  - *Dendritic Cells
MH  - *T-Lymphocytes
MH  - Immunosuppressive Agents/pharmacology
MH  - Immune Tolerance
MH  - Dexamethasone/pharmacology/metabolism
PMC - PMC10650502
OTO - NOTNLM
OT  - MERTK
OT  - dendritic cells
OT  - dexamethasone
OT  - efferocytosis
OT  - immune tolerance
COIS- The authors declare no conflict of interest.
EDAT- 2023/11/14 06:43
MHDA- 2023/11/15 06:42
PMCR- 2023/11/02
CRDT- 2023/11/14 02:10
PHST- 2023/09/28 00:00 [received]
PHST- 2023/10/26 00:00 [revised]
PHST- 2023/10/31 00:00 [accepted]
PHST- 2023/11/15 06:42 [medline]
PHST- 2023/11/14 06:43 [pubmed]
PHST- 2023/11/14 02:10 [entrez]
PHST- 2023/11/02 00:00 [pmc-release]
AID - ijms242115903 [pii]
AID - ijms-24-15903 [pii]
AID - 10.3390/ijms242115903 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Nov 2;24(21):15903. doi: 10.3390/ijms242115903.