Reduced annexin A1 expression associates with disease severity and inflammation in multiple sclerosis patients

Alessandra Colamatteo, Elisa Maggioli, Rodrigo Azevedo Loiola, Madeeha Hamid Sheikh, Gaetano Calì, Dario Bruzzese, Giorgia Teresa Maniscalco, Diego Centonze, Fabio Buttari, Roberta Lanzillo, Francesco Perna, Bruno Zuccarelli, Maria Mottola, Silvana Cassano, Mario Galgani, Egle Solito, Veronica De Rosa

Research output: Contribution to journalArticle

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+CD252 conventional T and CD4+RORgt+ 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.

Original languageEnglish
Pages (from-to)1753-1765
Number of pages13
JournalJournal of Immunology
Volume203
Issue number7
DOIs
Publication statusPublished - Oct 1 2019

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Annexin A1
Annexins
Multiple Sclerosis
Inflammation
Th17 Cells
T-Lymphocytes
Relapsing-Remitting Multiple Sclerosis
Th1 Cells
Glycolysis
Blood-Brain Barrier
Glucocorticoids
Autoimmune Diseases
Disease Progression
Monocytes
Leukocytes
Cell Proliferation
Therapeutics
Proteins

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Colamatteo, A., Maggioli, E., Loiola, R. A., Sheikh, M. H., Calì, G., Bruzzese, D., ... De Rosa, V. (2019). Reduced annexin A1 expression associates with disease severity and inflammation in multiple sclerosis patients. Journal of Immunology, 203(7), 1753-1765. https://doi.org/10.4049/jimmunol.1801683

Reduced annexin A1 expression associates with disease severity and inflammation in multiple sclerosis patients. / Colamatteo, Alessandra; Maggioli, Elisa; Loiola, Rodrigo Azevedo; Sheikh, Madeeha Hamid; Calì, Gaetano; Bruzzese, Dario; Maniscalco, Giorgia Teresa; Centonze, Diego; Buttari, Fabio; Lanzillo, Roberta; Perna, Francesco; Zuccarelli, Bruno; Mottola, Maria; Cassano, Silvana; Galgani, Mario; Solito, Egle; De Rosa, Veronica.

In: Journal of Immunology, Vol. 203, No. 7, 01.10.2019, p. 1753-1765.

Research output: Contribution to journalArticle

Colamatteo, A, Maggioli, E, Loiola, RA, Sheikh, MH, Calì, G, Bruzzese, D, Maniscalco, GT, Centonze, D, Buttari, F, Lanzillo, R, Perna, F, Zuccarelli, B, Mottola, M, Cassano, S, Galgani, M, Solito, E & De Rosa, V 2019, 'Reduced annexin A1 expression associates with disease severity and inflammation in multiple sclerosis patients', Journal of Immunology, vol. 203, no. 7, pp. 1753-1765. https://doi.org/10.4049/jimmunol.1801683
Colamatteo, Alessandra ; Maggioli, Elisa ; Loiola, Rodrigo Azevedo ; Sheikh, Madeeha Hamid ; Calì, Gaetano ; Bruzzese, Dario ; Maniscalco, Giorgia Teresa ; Centonze, Diego ; Buttari, Fabio ; Lanzillo, Roberta ; Perna, Francesco ; Zuccarelli, Bruno ; Mottola, Maria ; Cassano, Silvana ; Galgani, Mario ; Solito, Egle ; De Rosa, Veronica. / Reduced annexin A1 expression associates with disease severity and inflammation in multiple sclerosis patients. In: Journal of Immunology. 2019 ; Vol. 203, No. 7. pp. 1753-1765.
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