TY - JOUR
T1 - Reduced annexin A1 expression associates with disease severity and inflammation in multiple sclerosis patients
AU - Colamatteo, Alessandra
AU - Maggioli, Elisa
AU - Loiola, Rodrigo Azevedo
AU - Sheikh, Madeeha Hamid
AU - Calì, Gaetano
AU - Bruzzese, Dario
AU - Maniscalco, Giorgia Teresa
AU - Centonze, Diego
AU - Buttari, Fabio
AU - Lanzillo, Roberta
AU - Perna, Francesco
AU - Zuccarelli, Bruno
AU - Mottola, Maria
AU - Cassano, Silvana
AU - Galgani, Mario
AU - Solito, Egle
AU - De Rosa, Veronica
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1801683
DO - 10.4049/jimmunol.1801683
M3 - Article
C2 - 31462505
AN - SCOPUS:85072627265
VL - 203
SP - 1753
EP - 1765
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 7
ER -