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Liver X receptor beta deficiency attenuates autoimmune-associated neuroinflammation in a T cell-dependent manner
- Source :
- Journal of autoimmunity, 124:102723. Academic Press Inc., Journal of Autoimmunity, 124:102723. Academic Press, Journal of Autoimmunity, 124:102723. Elsevier Science
- Publication Year :
- 2021
-
Abstract
- The initiation and progression of autoimmune disorders such as multiple sclerosis (MS) is linked to aberrant cholesterol metabolism and overt inflammation. Liver X receptors (LXR) are nuclear receptors that function at the crossroads of cholesterol metabolism and immunity, and their activation is considered a promising therapeutic strategy to attenuate autoimmunity. However, despite clear functional heterogeneity and cell-specific expression profiles, the impact of the individual LXR isoforms on autoimmunity remains poorly understood. Here, we show that LXR alpha and LXR beta have an opposite impact on immune cell function and disease severity in the experimental autoimmune encephalomyelitis model, an experimental MS model. While Lxr alpha deficiency aggravated disease pathology and severity, absence of Lxr beta was protective. Guided by flow cytometry and by using cell-specific knockout models, reduced disease severity in Lxr beta-deficient mice was primarily attributed to changes in peripheral T cell physiology and occurred independent from alterations in microglia function. Collectively, our findings indicate that LXR isoforms play functionally non-redundant roles in autoimmunity, potentially having broad implications for the development of LXR-based therapeutic strategies aimed at dampening autoimmunity and neuroinflammation.
- Subjects :
- Encephalomyelitis, Autoimmune, Experimental
T-Lymphocytes
T cell
Immunology
Inflammation
Autoimmunity
METABOLISM
medicine.disease_cause
Liver X receptors
Multiple sclerosis
MICROGLIA
Mice
Liver X receptor beta
INFLAMMATION
Animals
Humans
Immunology and Allergy
Medicine
Cholesterol metabolism
Liver X receptor
Neuroinflammation
GENE-EXPRESSION
Mice, Knockout
Immunometabolism
LXR-ALPHA
business.industry
CHOLESTEROL
Experimental autoimmune encephalomyelitis
TRANSREPRESSION
PATHWAYS
medicine.disease
Mice, Inbred C57BL
Disease Models, Animal
medicine.anatomical_structure
SUMOYLATION
Nuclear receptor
Neurogenic Inflammation
medicine.symptom
business
Subjects
Details
- Language :
- English
- ISSN :
- 08968411
- Volume :
- 124
- Database :
- OpenAIRE
- Journal :
- Journal of Autoimmunity
- Accession number :
- edsair.doi.dedup.....d2dd23def63f6dfbba5a9991a3724914