MicroRNA‑155 modulation of CD8<sup>+</sup> T‑cell activity personalizes response to disease‑modifying therapies of patients with relapsing‑remitting multiple sclerosis

Elkhodiry,Aya A.; Zamzam,Dina A.; El Tayebi,Hend M.

doi:10.3892/mi.2023.80

March-April 2023 Volume 3 Issue 2

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March-April 2023 Volume 3 Issue 2

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Article Open Access

MicroRNA‑155 modulation of CD8⁺ T‑cell activity personalizes response to disease‑modifying therapies of patients with relapsing‑remitting multiple sclerosis

Authors:
- Aya A. Elkhodiry
- Dina A. Zamzam
- Hend M. El Tayebi
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Affiliations: Molecular Pharmacology Research Group, Department of Pharmacology, Toxicology and Clinical Pharmacy, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt, Department of Neurology, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt

Copyright: © Elkhodiry et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 20
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Published online on: March 20, 2023

https://doi.org/10.3892/mi.2023.80
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Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease where activated immune cells can attack oligodendrocytes causing damage to the myelin sheath. Several molecular mechanisms are responsible for the auto‑activation of immune cells such as RNA interference (RNAi) through microRNAs (miRNAs or miRs). In the present study, the role of miR‑155 in regulating CD8⁺ T‑cell activity in patients with relapsing‑remitting multiple sclerosis (RRMS) was investigated, in terms of its migratory functions with regard to intracellular adhesion molecule‑1 (ICAM1) and integrin subunit β2 (ITGB2), and its cytotoxic proteins, perforin and granzyme B. Gene expression of miR‑155, ICAM1, ITGB2, perforin and granzyme B was evaluated following epigenetic modulations using reverse transcription‑quantitative polymerase chain reaction in CD8⁺ T-cells isolated from blood samples of patients with RRMS and compared to healthy controls. The ectopic expression of miR‑155 resulted in a persistent downregulation in all genes of interest related to CD8⁺ T‑cell activation that were positively correlated with the Expanded Disability Status Scale of patients. The present study revealed the interplay between miR‑155, ICAM1, and ITGB2, shedding light on their beneficial use as possible therapeutic regulators and diagnostic biomarkers of disease. Moreover, epigenetic modulations enhancing the efficacy of disease‑modifying therapies (DMTs) may be employed as personalized therapy, to decrease the side effects of DMTs and improve the outcomes of patients.

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