Back to Search
Start Over
Regulation of microglial TMEM119 and P2RY12 immunoreactivity in multiple sclerosis white and grey matter lesions is dependent on their inflammatory environment.
- Source :
-
Acta neuropathologica communications [Acta Neuropathol Commun] 2019 Dec 11; Vol. 7 (1), pp. 206. Date of Electronic Publication: 2019 Dec 11. - Publication Year :
- 2019
-
Abstract
- Multiple Sclerosis (MS) is the most common cause of acquired neurological disability in young adults, pathologically characterized by leukocyte infiltration of the central nervous system, demyelination of the white and grey matter, and subsequent axonal loss. Microglia are proposed to play a role in MS lesion formation, however previous literature has not been able to distinguish infiltrated macrophages from microglia. Therefore, in this study we utilize the microglia-specific, homeostatic markers TMEM119 and P2RY12 to characterize their immunoreactivity in MS grey matter lesions in comparison to white matter lesions. Furthermore, we assessed the immunological status of the white and grey matter lesions, as well as the responsivity of human white and grey matter derived microglia to inflammatory mediators. We are the first to show that white and grey matter lesions in post-mortem human material differ in their immunoreactivity for the homeostatic microglia-specific markers TMEM119 and P2RY12. In particular, whereas immunoreactivity for TMEM119 and P2RY12 is decreased in the center of WMLs, immunoreactivity for both markers is not altered in GMLs. Based on data from post-mortem human microglia cultures, treated with IL-4 or IFNγ+LPS and on  counts of CD3 <superscript>+</superscript> or CD20 <superscript>+</superscript> lymphocytes in lesions, we show that downregulation of TMEM119 and P2RY12  immunoreactivity in MS lesions corresponds with the presence of lymphocytes and lymphocyte-derived cytokines within the parenchyma but not in  the meninges. Furthermore, the presence of TMEM119 <superscript>+</superscript> and partly P2RY12 <superscript>+</superscript> microglia in pre-active lesions as well as in  the rim of active white and grey matter lesions, in addition to TMEM119 <superscript>+</superscript> and P2RY12 <superscript>+</superscript> rod-like microglia in subpial grey matter lesions suggest that blocking the entrance of lymphocytes into the CNS of MS patients may not interfere with all possible effects of TMEM119 <superscript>+</superscript> and P2RY12 <superscript>+</superscript> microglia in both white and grey matter MS lesions.
- Subjects :
- Adult
Aged
Aged, 80 and over
Female
Gray Matter chemistry
Gray Matter pathology
Humans
Inflammation metabolism
Inflammation pathology
Male
Membrane Proteins analysis
Microglia chemistry
Microglia pathology
Middle Aged
Multiple Sclerosis pathology
Receptors, Purinergic P2Y12 analysis
White Matter chemistry
White Matter pathology
Gray Matter metabolism
Membrane Proteins metabolism
Microglia metabolism
Multiple Sclerosis metabolism
Receptors, Purinergic P2Y12 metabolism
White Matter metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2051-5960
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Acta neuropathologica communications
- Publication Type :
- Academic Journal
- Accession number :
- 31829283
- Full Text :
- https://doi.org/10.1186/s40478-019-0850-z