Reduced Annexin A1 Expression Associates with Disease Severity and Inflammation in Multiple Sclerosis Patients.
J Immunol
; 203(7): 1753-1765, 2019 10 01.
Article
in En
| MEDLINE
| ID: mdl-31462505
ABSTRACT
Chronic neuroinflammation is a key pathological hallmark of multiple sclerosis (MS) that suggests that resolution of inflammation by specialized proresolving molecules is dysregulated in the disease. Annexin A1 (ANXA1) is a protein induced by glucocorticoids that facilitates resolution of inflammation through several mechanisms that include an inhibition of leukocyte recruitment and activation. In this study, we investigated the ability of ANXA1 to influence T cell effector function in relapsing/remitting MS (RRMS), an autoimmune disease sustained by proinflammatory Th1/Th17 cells. Circulating expression levels of ANXA1 in naive-to-treatment RRMS subjects inversely correlated with disease score and progression. At the cellular level, there was an impaired ANXA1 production by CD4+CD25- conventional T and CD4+RORγt+ T (Th17) cells from RRMS subjects that associated with an increased migratory capacity in an in vitro model of blood brain barrier. Mechanistically, ANXA1 impaired monocyte maturation secondarily to STAT3 hyperactivation and potently reduced T cell activation, proliferation, and glycolysis. Together, these findings identify impaired disease resolution pathways in RRMS caused by dysregulated ANXA1 expression that could represent new potential therapeutic targets in RRMS.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lymphocyte Activation
/
Gene Expression Regulation
/
Annexin A1
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Th1 Cells
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Th17 Cells
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Multiple Sclerosis
Type of study:
Clinical_trials
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
J Immunol
Year:
2019
Document type:
Article
Affiliation country: