Intestinal Permeability and Circulating CD161+CCR6+CD8+T Cells in Patients With Relapsing-Remitting Multiple Sclerosis Treated With Dimethylfumarate

Maria C Buscarinu; Francesca Gargano; Luana Lionetto; Matilde Capi; Emanuele Morena; Arianna Fornasiero; Roberta Reniè; Anna C Landi; Giulia Pellicciari; Carmela Romano; Rosella Mechelli; Silvia Romano; Giovanna Borsellino; Luca Battistini; Maurizio Simmaco; Corrado Fagnani; Marco Salvetti; Giovanni Ristori

doi:10.3389/fneur.2021.683398

Intestinal Permeability and Circulating CD161+CCR6+CD8+T Cells in Patients With Relapsing-Remitting Multiple Sclerosis Treated With Dimethylfumarate

Maria C Buscarinu, Francesca Gargano, Luana Lionetto, Matilde Capi, Emanuele Morena, Arianna Fornasiero, Roberta Reniè, Anna C Landi, Giulia Pellicciari, Carmela Romano, Rosella Mechelli, Silvia Romano, Giovanna Borsellino, Luca Battistini, Maurizio Simmaco, Corrado Fagnani, Marco Salvetti, Giovanni Ristori

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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.

Original language	English
Pages (from-to)	683398
Journal	Front. Neurol.
Volume	12
DOIs	https://doi.org/10.3389/fneur.2021.683398
Publication status	Published - 2021

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10.3389/fneur.2021.683398

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Buscarinu, M. C., Gargano, F., Lionetto, L., Capi, M., Morena, E., Fornasiero, A., Reniè, R., Landi, A. C., Pellicciari, G., Romano, C., Mechelli, R., Romano, S., Borsellino, G., Battistini, L., Simmaco, M., Fagnani, C., Salvetti, M., & Ristori, G. (2021). Intestinal Permeability and Circulating CD161+CCR6+CD8+T Cells in Patients With Relapsing-Remitting Multiple Sclerosis Treated With Dimethylfumarate. Front. Neurol., 12, 683398. https://doi.org/10.3389/fneur.2021.683398

Buscarinu, MC, Gargano, F, Lionetto, L, Capi, M, Morena, E, Fornasiero, A, Reniè, R, Landi, AC, Pellicciari, G, Romano, C, Mechelli, R, Romano, S, Borsellino, G, Battistini, L, Simmaco, M, Fagnani, C, Salvetti, M & Ristori, G 2021, 'Intestinal Permeability and Circulating CD161+CCR6+CD8+T Cells in Patients With Relapsing-Remitting Multiple Sclerosis Treated With Dimethylfumarate', Front. Neurol., vol. 12, pp. 683398. https://doi.org/10.3389/fneur.2021.683398

@article{5e4ed774c70c421cbb404127e99b43b8,

title = "Intestinal Permeability and Circulating CD161+CCR6+CD8+T Cells in Patients With Relapsing-Remitting Multiple Sclerosis Treated With Dimethylfumarate",

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.",

author = "Buscarinu, {Maria C} and Francesca Gargano and Luana Lionetto and Matilde Capi and Emanuele Morena and Arianna Fornasiero and Roberta Reni{\`e} and Landi, {Anna C} and Giulia Pellicciari and Carmela Romano and Rosella Mechelli and Silvia Romano and Giovanna Borsellino and Luca Battistini and Maurizio Simmaco and Corrado Fagnani and Marco Salvetti and Giovanni Ristori",

note = "Copyright {\textcopyright} 2021 Buscarinu, Gargano, Lionetto, Capi, Morena, Fornasiero, Reni{\`e}, Landi, Pellicciari, Romano, Mechelli, Romano, Borsellino, Battistini, Simmaco, Fagnani, Salvetti and Ristori.",

year = "2021",

doi = "10.3389/fneur.2021.683398",

language = "English",

volume = "12",

pages = "683398",

journal = "Front. Neurol.",

issn = "1664-2295",

publisher = "Frontiers Research Foundation",

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TY - JOUR

T1 - Intestinal Permeability and Circulating CD161+CCR6+CD8+T Cells in Patients With Relapsing-Remitting Multiple Sclerosis Treated With Dimethylfumarate

AU - Buscarinu, Maria C

AU - Gargano, Francesca

AU - Lionetto, Luana

AU - Capi, Matilde

AU - Morena, Emanuele

AU - Fornasiero, Arianna

AU - Reniè, Roberta

AU - Landi, Anna C

AU - Pellicciari, Giulia

AU - Romano, Carmela

AU - Mechelli, Rosella

AU - Romano, Silvia

AU - Borsellino, Giovanna

AU - Battistini, Luca

AU - Simmaco, Maurizio

AU - Fagnani, Corrado

AU - Salvetti, Marco

AU - Ristori, Giovanni

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.3389/fneur.2021.683398

DO - 10.3389/fneur.2021.683398

M3 - Article

C2 - 34512507

SN - 1664-2295

VL - 12

SP - 683398

JO - Front. Neurol.

JF - Front. Neurol.

ER -

Intestinal Permeability and Circulating CD161+CCR6+CD8+T Cells in Patients With Relapsing-Remitting Multiple Sclerosis Treated With Dimethylfumarate

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