Targeting miR-223 enhances myeloid-derived suppressor cell suppressive activities in multiple sclerosis patients

Authors

Claudia Cantoni, Department of Translational Neuroscience, Barrow Neurological Institute, Phoenix, AZ, 85013, United States. Electronic address: claudia.cantoni@barrowneuro.org.Follow
Laura Ghezzi, Department of Neurology, Washington University School of Medicine, St. Louis, MO, 63110, United States; Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy; Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy.
Jasmine Choi, Department of Neurology, Washington University School of Medicine, St. Louis, MO, 63110, United States.
Anne H. Cross, Department of Neurology, Washington University School of Medicine, St. Louis, MO, 63110, United States.
Laura Piccio, Department of Neurology, Washington University School of Medicine, St. Louis, MO, 63110, United States; Charles Perkins Centre, School of Medical Sciences, The University of Sydney, Sydney, NSW, Australia.

Document Type

Article

Abstract

BACKGROUND: Multiple sclerosis (MS) is an incurable autoimmune inflammatory demyelinating disease of the central nervous system. Several MS medications can modify disease course through effects on adaptive immune cells, while drugs targeting innate immunity are under investigation. Myeloid-derived suppressor cells (MDSCs) which arise during chronic inflammation, are defined by their T-cell immunosuppressive functions. MiR-223 modulates myeloid cell maturation and expansion, including MDSCs. METHODS: MDSCs isolated from healthy controls (HC) and people with MS (pwMS) were co-cultured with CD4+ T-cells to study their immunosuppressive activities in vitro. Cytokines and chemokines concentration were evaluated by Luminex assay in the serum of HC, pwMS, and other neuroinflammatory diseases and correlated with MDSC activities. RESULTS: MDSC suppressive functions are dysregulated in pwMS compared to HC, which was reversed by glucocorticoids (GC). GC specifically downregulated miR-223 levels in MDSCs and increased the expression of STAT3. In vitro assay showed that miR-223 inhibition enhanced MDSC suppressive activity, STAT3 dependently. By multiple linear regression analysis, we demonstrated that MDSC phosphorylated STAT3 was correlated with serum GM-CSF in HC and pwMS. CONCLUSIONS: These results suggest that miR-223 could be a therapeutic target for enhancing MDSC's suppressive activities as an alternative to GC.

Keywords

Glucocorticoids, Multiple sclerosis, Myeloid-derived suppressor cells, Neuroinflammation, miR-223

Medical Subject Headings

Humans; Myeloid-Derived Suppressor Cells (metabolism); Multiple Sclerosis (metabolism); Cytokines (metabolism); CD4-Positive T-Lymphocytes (metabolism); Immunosuppressive Agents; MicroRNAs (metabolism)

Publication Date

8-1-2023

Publication Title

Multiple sclerosis and related disorders

E-ISSN

2211-0356

Volume

76

First Page

104839

PubMed ID

37364375

Digital Object Identifier (DOI)

10.1016/j.msard.2023.104839

Recommended Citation

Cantoni, Claudia; Ghezzi, Laura; Choi, Jasmine; Cross, Anne H.; and Piccio, Laura, "Targeting miR-223 enhances myeloid-derived suppressor cell suppressive activities in multiple sclerosis patients" (2023). Translational Neuroscience. 2348.
https://scholar.barrowneuro.org/neurobiology/2348