Impact of fingolimod on CD4+ T cell subset and cytokine profile of relapsing remitting multiple sclerosis patients

Kürtüncü, Murat; Yılmaz, Vuslat; Akçay, Halil İbrahim; Türkoğlu, Recai; Altunrende, Burcu; Çınar, Suzan; Ulusoy, Canan; Gündüz, Tuncay; İçöz, Sema; Kasap, Mithat; Caliskan, Zeynep; Ötünç, Göktürk; Eraksoy, Mefküre; Tüzün, Erdem

doi:10.1016/j.jneuroim.2019.577065

Cited by 15 publications

(18 citation statements)

References 30 publications

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“…In vitro and in vivo studies are necessary to more precisely dismantle the mode of action of fingolimod on IL37 production. Previous studies on the immunopharmacological mode of action of this drug in RR-MS have shown that it increases in a non-specific fashion both proand anti-inflammatory cytokine-producing T helper subsets (IFN-γ, TNF-α, IL4, and IL10-producing CD4+ T cells) [58]. We also observed an increasing trend of IL37 level expression after steroid therapy.…”

Section: Discussionsupporting

confidence: 76%

In Silico and In Vivo Analysis of IL37 in Multiple Sclerosis Reveals Its Probable Homeostatic Role on the Clinical Activity, Disability, and Treatment with Fingolimod

et al. 2019

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We evaluated the in silico expression and circulating levels of interleukin (IL)37 in patients with different forms of multiple sclerosis (MS) and also upon treatment with different disease-modifying drugs. The combined interpretation of the resulting data strengthens and extends the current emerging concept that endogenous IL37 plays an important role in determining onset and progression of MS. The in silico analysis revealed that production of IL37 from cluster of differentiation (CD)4+ T cells from MS patients was reduced in vitro as compared to healthy controls. The analysis of the datasets also demonstrated that "higher" levels of IL37 production from PBMC entailed significant protection from MS relapses. In addition, the in vivo part of the study showed that IL37 was selectively augmented in the sera of MS patients during a relapse and that treatment with the high potency disease-modifying drug fingolimod significantly increased the frequency of patients with circulating blood levels of IL37 (6/9, 66%) as compared to patients receiving no treatment (n = 48) or platform therapy (n = 59) who had levels of IL37 below the limit of the sensitivity of the assay. This finding therefore anticipates that fingolimod may at least partially exert its beneficial effects in MS by upregulating the production of IL37.

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Section: Discussionsupporting

confidence: 76%

In Silico and In Vivo Analysis of IL37 in Multiple Sclerosis Reveals Its Probable Homeostatic Role on the Clinical Activity, Disability, and Treatment with Fingolimod

et al. 2019

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“…There was no difference in the percentage of NKT-like (CD3 + /CD56+) lymphocytes between MS (both RRMS and PPMS) and healthy subjects [33,34] as well as between various forms of MS (RRMS, PPMS, and SPMS) [25]. On the other hand, according to Jons et al, the percentage of NKT-like cells in both peripheral blood and bone marrow is significantly lower in MS patients compared to healthy subjects [35].…”

Section: Nkt-likementioning

confidence: 85%

NKT and NKT-like Cells in Autoimmune Neuroinflammatory Diseases—Multiple Sclerosis, Myasthenia Gravis and Guillain-Barre Syndrome

Zarobkiewicz

Morawska

Michalski

et al. 2021

IJMS

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NKT cells comprise three subsets—type I (invariant, iNKT), type II, and NKT-like cells, of which iNKT cells are the most studied subset. They are capable of rapid cytokine production after the initial stimulus, thus they may be important for polarisation of Th cells. Due to this, they may be an important cell subset in autoimmune diseases. In the current review, we are summarising results of NKT-oriented studies in major neurological autoimmune diseases—multiple sclerosis, myasthenia gravis, and Guillain-Barre syndrome and their corresponding animal models.

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“…In another study, MAPK8 was related to the release of BECN1 form its complex with BCL2 apoptosis regulator (BCL2), which in turn results in macrophages, an important class of antigen-presenting cells that activated adaptive immune responses autophagy [31] . Besides, it is reported that Fingolimod can increase the C-C motif chemokine ligand 5 (CCL5) in peripheral blood to inhibit the egress of lymphocyte involved in antigen presentation, which restrain B cells for humoral immunity [32] . As the same result, Sullivan et al demonstrated endogenous CCL5 had a neutralization effect and inhibited B cell proliferation and IgM secretion when B cells stimulation [33] .…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, the activation of MAPK8 in T cells can inhibit the proliferation and in ltration due to neutralization. Additionally, the misbalanced level of chemokines like CCL5 is associated with the activation and function of cytotoxic T lymphocytes and may constrain CD8 + T cell out of lymphoid organs [32,37] . Furthermore, it is reported that HMGB1 can recruits cells across endothelial barriers and induced the production of tumor-necrosis (TNF) and interferon, which is an nuclear weapon in the immune arsenal [38] .…”

Section: Discussionmentioning

confidence: 99%

Noninvasive Identification of Core Gene Biomarkers in Patients with Acute Kidney Transplant Rejection

Zhao

2020

Preprint

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Background: Acute rejection (AR) is one of common and critical complications after kidney transplantation, which gives rise to an increasing of allograft loss and even death. However, the potential mechanisms of AR remain incompletely understood at present. This study aimed to reveal the underlying mechanisms and identify core biomarkers of AR.Methods: The AR gene expression profile GSE1563 involving 6 renal transplant patients undergoing AR and 9 patients with well-functioning transplant with no clinical evidence of rejection was selected to analyze the differentially expressed genes (DEGs) from purified RNA of peripheral blood lymphocytes. DAVID was used to carry out Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A protein-protein interaction (PPI) network was built to display the interactions among these DEGs. To get further reliable significant genes and mechanisms, gene set enrichment analysis (GSEA) was applied to evaluate the hub gene analyzing via PPI network.Results: A total of 347 DEGs were captured, including 301 upregulated genes and 46 downregulated genes. Go and KEGG pathway analysis showed the DEGs were particularly enriched in immune response, inflammatory response to antigenic stimulus, RNA transport and protein stabilization. The PPI network indicated 3 modules were also mainly involved in immune response and RNA transport. 18 hub genes were selected in PPI network, among which there were 6 core genes evaluated by DAVID. By the way of GSEA, Oxidative stress was another potential mechanism besides immunity and ncRNA transport. Conclusion: Our analysis uncovered the immune response including humoral and cellular immunity, ncRNA transport as well as oxidative stress was the major mechanisms of AR associated respectively with MAPK8, CCL5, HMGB1, NCBP2, XPO1 and APP, which could be novel noninvasive biomarkers in peripheral blood for early diagnosis and could be helpful to the treatment of AR.

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Impact of fingolimod on CD4+ T cell subset and cytokine profile of relapsing remitting multiple sclerosis patients

Cited by 15 publications

References 30 publications

In Silico and In Vivo Analysis of IL37 in Multiple Sclerosis Reveals Its Probable Homeostatic Role on the Clinical Activity, Disability, and Treatment with Fingolimod

In Silico and In Vivo Analysis of IL37 in Multiple Sclerosis Reveals Its Probable Homeostatic Role on the Clinical Activity, Disability, and Treatment with Fingolimod

NKT and NKT-like Cells in Autoimmune Neuroinflammatory Diseases—Multiple Sclerosis, Myasthenia Gravis and Guillain-Barre Syndrome

Noninvasive Identification of Core Gene Biomarkers in Patients with Acute Kidney Transplant Rejection

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