CD169 is a marker for highly pathogenic phagocytes in multiple sclerosis.

Autor: Bogie JF; Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium/School of Life Sciences, Transnationale Universiteit Limburg, Diepenbeek, Belgium., Boelen E; Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium/School of Life Sciences, Transnationale Universiteit Limburg, Diepenbeek, Belgium., Louagie E; Department of Rheumatology, Ghent University Hospital, Ghent, Belgium/Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Center, Ghent University, Ghent, Belgium., Delputte P; Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium., Elewaut D; Department of Rheumatology, Ghent University Hospital, Ghent, Belgium/Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Center, Ghent University, Ghent, Belgium., van Horssen J; Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium/School of Life Sciences, Transnationale Universiteit Limburg, Diepenbeek, Belgium/Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands., Hendriks JJ; Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium/School of Life Sciences, Transnationale Universiteit Limburg, Diepenbeek, Belgium., Hellings N; Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium/School of Life Sciences, Transnationale Universiteit Limburg, Diepenbeek, Belgium.
Jazyk: angličtina
Zdroj: Multiple sclerosis (Houndmills, Basingstoke, England) [Mult Scler] 2018 Mar; Vol. 24 (3), pp. 290-300. Date of Electronic Publication: 2017 Mar 09.
DOI: 10.1177/1352458517698759
Abstrakt: Background: Phagocytes, such as macrophages and microglia, are key effector cells in the pathophysiology of multiple sclerosis (MS). It is widely accepted that they instigate and promote neuroinflammatory and neurodegenerative events in MS. An increasing amount of studies indicate that Siglec-1, also known CD169, is a marker for activated phagocytes in inflammatory disorders.
Objective: In this study, we set out to define how CD169 + phagocytes contribute to neuroinflammation in MS.
Methods: CD169-diphtheria toxin receptor (DTR) mice, which express human DTR under control of the CD169 promoter, were used to define the impact of CD169 + cells on neuroinflammation. Flow cytometry and immunohistochemistry were utilized to determine the expression and distribution of CD169.
Results: We show that CD169 is highly expressed by lesional and circulating phagocytes in MS and experimental autoimmune encephalomyelitis (EAE). Our data further indicate that CD169 represents a selective marker for early activated microglia in MS and EAE lesions. Depletion of CD169 + cells markedly reduced neuroinflammation and ameliorated disease symptoms in EAE-affected mice.
Conclusion: Our findings indicate that CD169 + cells promote neuroinflammation. Furthermore, they suggest that CD169 + phagocytes play a key role in the pathophysiology of MS. Hence, targeting CD169 + phagocytes may hold therapeutic value for MS.
Databáze: MEDLINE