The immune imbalance between follicular regulatory and helper T cells in myelin oligodendrocyte glycoprotein IgG-associated disease

Xuechun Chang; Kexin Jiao; Danjie Wang; Yufan Zhou; Zhao Zhao; Ying Xing; Jingzi Zhangbao; Chuanzhen Lu; Jun Wang; Chao Quan

doi:10.1016/j.clim.2023.109734

The immune imbalance between follicular regulatory and helper T cells in myelin oligodendrocyte glycoprotein IgG-associated disease

Clin Immunol. 2023 Oct:255:109734. doi: 10.1016/j.clim.2023.109734. Epub 2023 Aug 11.

Authors

Xuechun Chang¹, Kexin Jiao¹, Danjie Wang², Yufan Zhou¹, Zhao Zhao³, Ying Xing⁴, Jingzi Zhangbao¹, Chuanzhen Lu¹, Jun Wang⁵, Chao Quan⁶

Affiliations

¹ Department of Neurology, National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, 12 Wulumuqi Road (Mid), Shanghai 200040, China.
² Department of Integrative Medicine and Neurobiology, School of Basic Medical Science, Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
³ Department of Pharmacy, Huashan Hospital, Shanghai Medical College, Fudan University, 12 Wulumuqi Road (Mid), Shanghai 200040, China.
⁴ Department of Rehabilitation Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, 12 Wulumuqi Road (Mid), Shanghai 200040, China.
⁵ Department of Integrative Medicine and Neurobiology, School of Basic Medical Science, Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China. Electronic address: jwangf@shmu.edu.cn.
⁶ Department of Neurology, National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, 12 Wulumuqi Road (Mid), Shanghai 200040, China. Electronic address: chao_quan@fudan.edu.cn.

PMID: 37572951
DOI: 10.1016/j.clim.2023.109734

Abstract

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a newly defined inflammatory demyelinating disease of the central nervous system. Currently, no immuno-modulatory treatment has been approved for MOGAD. We explored the function of follicular regularoty T (Tfr) and follicular helper T (Tfh) cells in patients with MOGAD. The number of circulating Tfr and Tfh cells and their expression of functional markers were accessed by flow cytometry. Circulating Tfr, Tfh, and B cells were further sorted and co-cultured in vitro to examine the influence of Tfr on Tfh-mediated B cell differentiation. In patients with MOGAD, the percentage of circulating PD-1^hi Tfh cells elevated while the frequency of circulating activated Tfr cells decreased significantly. The Tfh/Tfr ratios positively correlated with the percentage of plasmblasts. In vitro, Tfh cells from patients with MOGAD exhibited a stronger capacity to promote the differentiation of plasmablasts through producing interleukin (IL)-21 than non-Tfh cells from patients, whereas Tfr cells suppressed this Tfh-mediated plasmablasts expansion, to a similar extent of IL-1 receptor antagonist (IL-1Ra). In conclusion, we revealed an immune imbalance of Tfr and Tfh cells in MOGAD. Tfr and IL-1Ra could be potential therapeutic targets in MOGAD.

Keywords: B cell; Follicular helper T cell; Follicular regulatory T cell; Myelin oligodendrocyte glycoprotein.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

B-Lymphocytes
Humans
Immunoglobulin G / metabolism
Interleukin 1 Receptor Antagonist Protein*
Myelin-Oligodendrocyte Glycoprotein
T-Lymphocytes, Helper-Inducer*
T-Lymphocytes, Regulatory

Substances

Myelin-Oligodendrocyte Glycoprotein
Interleukin 1 Receptor Antagonist Protein
Immunoglobulin G