AUTHOR=Buscarinu Maria C. , Gargano Francesca , Lionetto Luana , Capi Matilde , Morena Emanuele , Fornasiero Arianna , Reniè Roberta , Landi Anna C. , Pellicciari Giulia , Romano Carmela , Mechelli Rosella , Romano Silvia , Borsellino Giovanna , Battistini Luca , Simmaco Maurizio , Fagnani Corrado , Salvetti Marco , Ristori Giovanni TITLE=Intestinal Permeability and Circulating CD161+CCR6+CD8+T Cells in Patients With Relapsing–Remitting Multiple Sclerosis Treated With Dimethylfumarate JOURNAL=Frontiers in Neurology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.683398 DOI=10.3389/fneur.2021.683398 ISSN=1664-2295 ABSTRACT=

Background: The changes of the gut-brain axis have been recently recognized as important components in multiple sclerosis (MS) pathogenesis.

Objectives: To evaluate the effects of DMF on intestinal barrier permeability and mucosal immune responses.

Methods: We investigated intestinal permeability (IP) and circulating CD161+CCR6+CD8+T cells in 25 patients with MS, who met eligibility criteria for dimethyl-fumarate (DMF) treatment. These data, together with clinical/MRI parameters, were studied at three time-points: baseline (before therapy), after one (T1) and 9 months (T2) of treatment.

Results: At baseline 16 patients (64%) showed altered IP, while 14 cases (56%) showed active MRI. During DMF therapy we found the expected decrease of disease activity at MRI compared to T0 (6/25 at T1, p = 0.035 and 3/25 at T2, p < 0.00), and a reduction in the percentage of CD161+CCR6+CD8+ T cells (16/23 at T2; p < 0.001). The effects of DMF on gut barrier alterations was variable, without a clear longitudinal pattern, while we found significant relationships between IP changes and drop of MRI activity (p = 0.04) and circulating CD161+CCr6+CD8+ T cells (p = 0.023).

Conclusions: The gut barrier is frequently altered in MS, and the CD161+ CCR6+CD8+ T cell-subset shows dynamics which correlate with disease course and therapy.