CCR6 blockade on regulatory T cells ameliorates experimental model of multiple sclerosis

Izabela Jatczak-Pawlik; Paweł Wolinski; Dominika Książek-Winiarek; Mirosława Pietruczuk; Andrzej Glabinski

doi:10.5114/ceji.2020.101241

eISSN: 1644-4124
ISSN: 1426-3912

Central European Journal of Immunology

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3/2020
vol. 45

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abstract:

Experimental immunology

CCR6 blockade on regulatory T cells ameliorates experimental model of multiple sclerosis

Izabela Jatczak-Pawlik

¹

,

Paweł Wolinski

¹

,

Dominika Książek-Winiarek

²

,

Mirosława Pietruczuk

³

,

Andrzej Glabinski

^{1, 2}

Department of Propedeutics of Neurology, Medical University of Lodz, Poland
Department of Neurology and Stroke, Medical University of Lodz, Poland
Department of Laboratory Medicine, Medical University of Lodz, Poland

Cent Eur J Immunol 2020; 45 (3): 256-266

DOI: https://doi.org/10.5114/ceji.2020.101241

Online publish date: 2020/11/01

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Regulatory T cells (Tregs) play a significant role in limiting damage of tissue affected by autoimmune process, which has been demonstrated in various experimental models for multiple sclerosis (MS) (mostly experimental autoimmune encephalomyelitis – EAE), rheumatoid arthritis, and type 1 diabetes. In this study, we demonstrated that Tregs increasingly migrate to central nervous system (CNS) during subsequent phases of EAE (preclinical, initial attack, and remission). In contrast, in peripheral tissues (blood, lymph nodes, and spleen), a significant accumulation of Tregs is mostly present during EAE remission. Moreover, an increased expression of CCR6 on Tregs in the CNS, blood, lymph nodes, and spleen in all phases of EAE was observed. The highest expression of CCR6 on Tregs from the CNS, lymph nodes, and spleen was noted during the initial attack of EAE, whereas in the blood, the peak expression of CCR6 was detected during the preclinical phase. The presence of Tregs in the CNS during EAE was confirmed by immunohistochemistry. To analyze additional functional significance of CCR6 expression on Tregs for EAE pathology, we modulated the clinical course of this MS model using Tregs with blocked CCR6. EAE mice, which received CCR6-deficient Tregs showed significant amelioration of disease severity. This observation suggests that CCR6 on Tregs may be a potential target for future therapeutic interventions in MS.

keywords:

CCR6 blockade on regulatory T cells ameliorates experimental model of multiple sclerosis

Izabela Jatczak-Pawlik 1 , Paweł Wolinski 1 , Dominika Książek-Winiarek 2 , Mirosława Pietruczuk 3 , Andrzej Glabinski 1, 2

multiple sclerosis, Tregs, CCR6, experimental autoimmune encephalomyelitis, anti-CCR6

Izabela Jatczak-Pawlik

¹

,

Paweł Wolinski

¹

,

Dominika Książek-Winiarek

²

,

Mirosława Pietruczuk

³

,

Andrzej Glabinski

^{1, 2}