Increased IL-2 and reduced tgf-? upon t-cell stimulation are associated with GM-CSF upregulation in multiple immune cell types in multiple sclerosis

Aram, Jehan; Frakich, Nanci; Morandi, Elena; Alrouji, Mohammed; Samaraweera, Amal; Onion, David; Spendlove, Ian; Colombo, Sergio L.; Tanasescu, Radu; Gran, Bruno; Constantinescu, Cris S.

Abstract

© 2020 by the authors. Granulocyte macrophage colony stimulating factor (GM-CSF) is a pro-inflammatory cytokine produced by immune cells. Recent evidence suggests that GM-CSF plays an important role in multiple sclerosis (MS) pathogenesis. We investigated the expression and regulation of GM-CSF in different immune cells in MS. We also investigated the differentiation and frequency of GM-CSF-producing Th cells that do not co-express interferon (IFN)-γ or interleukin-17 (IL-17) (Th-GM cells) in MS. We found a significant increase in the percentage of GM-CSF-expressing Th cells, Th1 cells, Th-GM cells, cytotoxic T (Tc) cells, monocytes, natural killer (NK) cells, and B cells in PBMC from MS patients stimulated with T cell stimuli. Stimulated PBMC culture supernatants from MS patients contained significantly higher levels of IL-2, IL-12, IL-1β, and GM-CSF and significantly lower levels of transforming growth factor (TGF-)β. Blocking IL-2 reduced the frequency of Th-GM cells in PBMC from MS patients. The frequency of Th-GM cells differentiated in vitro from naive CD4+ T cells was significantly higher in MS patients and was further increased in MS with IL-2 stimulation. These findings suggest that all main immune cell subsets produce more GM-CSF in MS after in vitro stimulation, which is associated with defective TGF-β and increased IL-2 and IL-12 production. Th-GM cells are increased in MS. GM-CSF may be a potential therapeutic target in MS.

Citation

Aram, J., Frakich, N., Morandi, E., Alrouji, M., Samaraweera, A., Onion, D., …Constantinescu, C. S. (2020). Increased IL-2 and reduced tgf-β upon t-cell stimulation are associated with GM-CSF upregulation in multiple immune cell types in multiple sclerosis. Biomedicines, 8(7), https://doi.org/10.3390/BIOMEDICINES8070226

• Journal Article Type: Article
• Acceptance Date: Jul 16, 2020
• Online Publication Date: Jul 18, 2020
• Publication Date: Jul 18, 2020
• Deposit Date: Jul 24, 2020
• Publicly Available Date: Jul 28, 2020
• Journal: Biomedicines
• Electronic ISSN: 2227-9059
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 7
• Article Number: 226
• DOI: https://doi.org/10.3390/BIOMEDICINES8070226
• Public URL: https://nottingham-repository.worktribe.com/output/4786080
• Publisher URL: https://www.mdpi.com/2227-9059/8/7/226