Open AccessMethylprednisolone alleviates multiple sclerosis by expanding myeloid‐derived suppressor cells via glucocorticoid receptor β and S100A8/9 up‐regulation
Author(s) -
Wang Zhongkun,
Zheng Ge,
Li Guangjian,
Wang Mengkun,
Ma Zhanchuan,
Li Huimin,
Wang XiangYang,
Yi Huanfa
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15928
Subject(s) - methylprednisolone , glucocorticoid receptor , multiple sclerosis , glucocorticoid , immune system , myeloid derived suppressor cell , myeloid , medicine , immunology , pharmacology , neuroblastoma , downregulation and upregulation , dexamethasone , cancer research , chemistry , suppressor , biology , cancer , biochemistry , gene , genetics , cell culture
Methylprednisolone is an effective drug in the treatment of autoimmune disease, such as multiple sclerosis (MS), due to long‐acting anti‐inflammatory, antiallergic and immunosuppressant. Previous studies have noted the importance of myeloid‐derived suppressor cells (MDSC) in MS progression. However, it is still not known whether methylprednisolone could influence the ratio and function of MDSC during MS treatment. In the current study, we found an increased ratio of MDSC at the onset of EAE in mice model; but methylprednisolone pulse therapy (MPPT) did not alter the percentage and suppressive function of MDSC during disease attenuation. However, the percentage of G‐MDSC in PBMC significantly increased in patients with MS. Surprisingly, relapsing MS patients showed a significant increase in both M‐MDSC and G‐MDSC after MPPT. The disease remission positively correlated expansion of MDSC and expression of arginase‐1. Additionally, MPPT reduced the expression of inhibitory glucocorticoid (GCs) receptor β subunit on MDSC while elevating serum levels of immune regulatory S100A8/A9 heterodimer. Thus, MDSC dynamics and function in mouse EAE differ from those in human MS during MPPT. Our study suggested that GCs treatment may help relieve the acute phase of MS by expanding MDSC through up‐regulating of GR signalling and S100A8/A9 heterodimers.