PMID- 32718316
OWN - NLM
STAT- MEDLINE
DCOM- 20210604
LR  - 20210604
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 17
IP  - 1
DP  - 2020 Jul 27
TI  - CD36-mediated uptake of myelin debris by macrophages and microglia reduces 
      neuroinflammation.
PG  - 224
LID - 10.1186/s12974-020-01899-x [doi]
LID - 224
AB  - BACKGROUND: The presence of foamy macrophages and microglia containing 
      intracellular myelin remnants is a pathological hallmark of neurodegenerative 
      disorders such as multiple sclerosis (MS). Despite the importance of myelin 
      internalization in affecting both central nervous system repair and 
      neuroinflammation, the receptors involved in myelin clearance and their impact on 
      the phagocyte phenotype and lesion progression remain to be clarified. METHODS: 
      Flow cytometry, quantitative PCR, and immunohistochemistry were used to define 
      the mRNA and protein abundance of CD36 in myelin-containing phagocytes. The 
      impact of CD36 and nuclear factor erythroid 2-related factor 2 (NRF2) on the 
      phagocytic and inflammatory features of macrophages and microglia was assessed 
      using a pharmacological CD36 inhibitor (sulfo-N-succinimidyl oleate) and 
      Nrf2(-/-) bone marrow-derived macrophages. Finally, the experimental autoimmune 
      encephalomyelitis (EAE) model was used to establish the impact of CD36 inhibition 
      on neuroinflammation and myelin phagocytosis in vivo. RESULTS: Here, we show that 
      the fatty acid translocase CD36 is required for the uptake of myelin debris by 
      macrophages and microglia, and that myelin internalization increased CD36 
      expression through NRF2. Pharmacological inhibition of CD36 promoted the 
      inflammatory properties of myelin-containing macrophages and microglia in vitro, 
      which was paralleled by a reduced activity of the anti-inflammatory lipid-sensing 
      liver X receptors and peroxisome proliferator-activated receptors. By using the 
      EAE model, we provide evidence that CD36 is essential for myelin debris clearance 
      in vivo. Importantly, CD36 inhibition markedly increased the neuroinflammatory 
      burden and disease severity in the EAE model. CONCLUSION: Altogether, we show for 
      the first time that CD36 is crucial for clearing myelin debris and suppressing 
      neuroinflammation in demyelinating disorders such as MS.
FAU - Grajchen, Elien
AU  - Grajchen E
AD  - Department of Immunology and Infection, Biomedical Research Institute, Hasselt 
      University, Diepenbeek, Belgium.
FAU - Wouters, Elien
AU  - Wouters E
AD  - Department of Immunology and Infection, Biomedical Research Institute, Hasselt 
      University, Diepenbeek, Belgium.
FAU - van de Haterd, Britt
AU  - van de Haterd B
AD  - Department of Immunology and Infection, Biomedical Research Institute, Hasselt 
      University, Diepenbeek, Belgium.
FAU - Haidar, Mansour
AU  - Haidar M
AD  - Department of Immunology and Infection, Biomedical Research Institute, Hasselt 
      University, Diepenbeek, Belgium.
FAU - Hardonniere, Kevin
AU  - Hardonniere K
AD  - Inflammation, Microbiome and Immunosurveillance, INSERM UMR99, Universite 
      Paris-Saclay, Chatenay-Malabry, France.
FAU - Dierckx, Tess
AU  - Dierckx T
AD  - Department of Immunology and Infection, Biomedical Research Institute, Hasselt 
      University, Diepenbeek, Belgium.
FAU - Van Broeckhoven, Jana
AU  - Van Broeckhoven J
AD  - Department of Immunology and Infection, Biomedical Research Institute, Hasselt 
      University, Diepenbeek, Belgium.
FAU - Erens, Celine
AU  - Erens C
AD  - Department of Immunology and Infection, Biomedical Research Institute, Hasselt 
      University, Diepenbeek, Belgium.
FAU - Hendrix, Sven
AU  - Hendrix S
AD  - Department of Immunology and Infection, Biomedical Research Institute, Hasselt 
      University, Diepenbeek, Belgium.
FAU - Kerdine-Romer, Saadia
AU  - Kerdine-Romer S
AD  - Inflammation, Microbiome and Immunosurveillance, INSERM UMR99, Universite 
      Paris-Saclay, Chatenay-Malabry, France.
FAU - Hendriks, Jerome J A
AU  - Hendriks JJA
AD  - Department of Immunology and Infection, Biomedical Research Institute, Hasselt 
      University, Diepenbeek, Belgium.
FAU - Bogie, Jeroen F J
AU  - Bogie JFJ
AUID- ORCID: 0000-0002-0016-1926
AD  - Department of Immunology and Infection, Biomedical Research Institute, Hasselt 
      University, Diepenbeek, Belgium. Jeroen.bogie@uhasselt.be.
LA  - eng
GR  - 12J9116N, 12JG119N, 12U7718N, and G099618N/Fonds Wetenschappelijk Onderzoek/
GR  - FCS-2016-EG7, R-8676, and R-6832/Belgian Charcot Foundation/
PT  - Journal Article
DEP - 20200727
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (CD36 Antigens)
SB  - IM
MH  - Animals
MH  - CD36 Antigens/*metabolism
MH  - Encephalomyelitis, Autoimmune, Experimental/metabolism/pathology
MH  - Female
MH  - Inflammation/metabolism/pathology
MH  - Macrophages/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microglia/*metabolism
MH  - Myelin Sheath/*metabolism
MH  - Phagocytosis/*physiology
PMC - PMC7384221
OTO - NOTNLM
OT  - CD36
OT  - Fatty acid
OT  - Macrophages
OT  - Microglia
OT  - Multiple sclerosis
OT  - Myelin
OT  - Neuroinflammation
COIS- The authors declare that they have no competing interests.
EDAT- 2020/07/29 06:00
MHDA- 2021/06/05 06:00
PMCR- 2020/07/27
CRDT- 2020/07/29 06:00
PHST- 2020/03/12 00:00 [received]
PHST- 2020/07/15 00:00 [accepted]
PHST- 2020/07/29 06:00 [entrez]
PHST- 2020/07/29 06:00 [pubmed]
PHST- 2021/06/05 06:00 [medline]
PHST- 2020/07/27 00:00 [pmc-release]
AID - 10.1186/s12974-020-01899-x [pii]
AID - 1899 [pii]
AID - 10.1186/s12974-020-01899-x [doi]
PST - epublish
SO  - J Neuroinflammation. 2020 Jul 27;17(1):224. doi: 10.1186/s12974-020-01899-x.