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Cellular and Molecular Life Sciences

, Volume 75, Issue 17, pp 3099–3120 | Cite as

The potential importance of myeloid-derived suppressor cells (MDSCs) in the pathogenesis of Alzheimer’s disease

  • Antero Salminen
  • Kai Kaarniranta
  • Anu Kauppinen
Review

Abstract

The exact cause of Alzheimer’s disease (AD) is still unknown, but the deposition of amyloid-β (Aβ) plaques and chronic inflammation indicates that immune disturbances are involved in AD pathogenesis. Recent genetic studies have revealed that many candidate genes are expressed in both microglia and myeloid cells which infiltrate into the AD brains. Invading myeloid cells controls the functions of resident microglia in pathological conditions, such as AD pathology. AD is a neurologic disease with inflammatory component where the immune system is not able to eliminate the perpetrator, while, concurrently, it should prevent neuronal injuries induced by inflammation. Recent studies have indicated that AD brains are an immunosuppressive microenvironment, e.g., microglial cells are hyporesponsive to Aβ deposits and anti-inflammatory cytokines enhance Aβ deposition. Immunosuppression is a common element in pathological disorders involving chronic inflammation. Studies on cancer-associated inflammation have demonstrated that myeloid-derived suppressor cells (MDSCs) have a crucial role in the immune escape of tumor cells. Immunosuppression is not limited to tumors, since MDSCs can be recruited into chronically inflamed tissues where inflammatory mediators enhance the proliferation and activation of MDSCs. AD brains express a range of chemokines and cytokines which could recruit and expand MDSCs in inflamed AD brains and thus generate an immunosuppressive microenvironment. Several neuroinflammatory disorders, e.g., the early phase of AD pathology, have been associated with an increase in the level of circulating MDSCs. We will elucidate the immunosuppressive armament of MDSCs and present evidences in support of the crucial role of MDSCs in the pathogenesis of AD.

Keywords

Aging Alzheimer Hypoxia Neuroinflammation NF-κB Senescence 

Abbreviations

Amyloid-β

AD

Alzheimer’s disease

APP

Amyloid precursor protein

ARG1

Arginase 1

Breg

Regulatory B cell

CAA

Cerebral amyloid angiopathy

C/EBPβ

CCAAT/enhancer-binding protein β

CHOP

C/EBP-homologous protein

FOXP3

Forkhead box P3

GCN2

General control nonderepressible 2 kinase

HIF-1α

Hypoxia-inducible factor-1α

HMGB1

High mobility group box 1

HSV1

Herpes simplex virus type 1

IDO

Indoleamine-pyrrole 2,3-dioxygenase

MCI

Mild cognitive impairment

MDSC

Myeloid-derived suppressor cell

MIF

Macrophage migration inhibitory factor

NF-κB

Nuclear factor-κB

NO

Nitric oxide

NOS

Nitric oxide synthase

NOX2

NADPH2 oxidase 2

NRF2

Nuclear factor-erythroid 2-related factor 2

NSAID

Non-steroidal anti-inflammatory drug

PD-L1

Programmed death-ligand 1

PGE2

Prostaglandin E2

STAT

Signal transducer and activator of transcription

TGF-β

Transforming growth factor-β

TNF-α

Tumor necrosis factor-α

Treg

Regulatory T cell

TREM2

Triggering receptor expressed on myeloid cells 2

Notes

Acknowledgements

This study was financially supported by the Grants from the Terveyden Tutkimuksen Toimikunta of Academy of Finland (AK297267, AK307341, and KK296840), the Kuopio University Hospital VTR Grant (KK5503743), the Emil Aaltonen Foundation, the Finnish Cultural Foundation, and the Finnish Eye Foundation. The authors thank Dr. Ewen MacDonald for checking the language of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors state that there are no personal or institutional conflicts of interest.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Antero Salminen
    • 1
  • Kai Kaarniranta
    • 2
    • 3
  • Anu Kauppinen
    • 4
  1. 1.Department of Neurology, Institute of Clinical MedicineUniversity of Eastern FinlandKuopioFinland
  2. 2.Department of Ophthalmology, Institute of Clinical MedicineUniversity of Eastern FinlandKuopioFinland
  3. 3.Department of OphthalmologyKuopio University HospitalKuopioFinland
  4. 4.School of Pharmacy, Faculty of Health SciencesUniversity of Eastern FinlandKuopioFinland

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