CD93 regulates CNS inflammation in two mouse models of autoimmune encephalomyelitis
File(s)
Accepted version
Author(s)
Griffiths, Mark R
Botto, Marina
Morgan, B Paul
Neal, JW
Gasque, P
Type
Journal Article
Abstract
Microglia and non-professional immune cells (endothelial cells, neurons) participate in the recognition and removal of pathogens and tissue-debris in the injured CNS through major pro-inflammatory processes. However, the mechanisms involved in regulating these responses remain ill-characterised. We herein show that CD93 also known as complement C1qRp/AA4 stem cell marker has an important role in the regulation of inflammatory processes. The role of CD93 was evaluated in two models of neuroinflammation. We used the MOG-experimental autoimmune encephalomyelitis (EAE) model and the antibody-dependent EAE (ADEAE) which were induced in wild type and CD93 knockout mice. We found that CD93 was highly expressed by neurons, endothelial cells and microglia (ramified > amoeboid). Astrocytes and oligodendrocytes did not to express CD93. We further observed that CD93 deficient (CD93-/-) mice presented a more robust brain and spinal cord inflammation in EAE and ADEAE. Encephalitis in CD93-/- was characterized by increased numbers of infiltrating M1 macrophages (CD11c+ CD206-) and amoeboid microglia exhibiting a more activated phenotype (Tomato Lectinhigh , Cox2high ). Damage and leakage of the blood brain barrier was increased in CD93-/- animals and was associated with a more robust neuronal injury when compared to wild type EAE mice. We propose that CD93 is an important neuro-immune regulator (NIREG) to control CNS inflammation.
Date Issued
2018-11-01
Date Acceptance
2018-06-01
Citation
Immunology, 2018, 155 (3), pp.346-355
ISSN
0019-2805
Publisher
Wiley
Start Page
346
End Page
355
Journal / Book Title
Immunology
Volume
155
Issue
3
Copyright Statement
© 2018 John Wiley & Sons Ltd. All rights reserved. This is the accepted version of the following article: Griffiths, M. R., Botto, M. , Morgan, B. P., Neal, J. W. and Gasque, P. (2018), CD93 regulates CNS inflammation in two mouse models of autoimmune encephalomyelitis. Immunology. Accepted Author Manuscript. . doi:10.1111/imm.12974, which has been published in final form at https://dx.doi.org/10.1111/imm.12974
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/29923617
Subjects
NIREG
CD93
complement
innate immunity
multiple sclerosis
neuroinflammation
neurons
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2018-06-20