Disrupted balance of T cells under natalizumab treatment in multiple sclerosis

Kimura, Kimitoshi; Nakamura, Masakazu; Sato, Wakiro; Okamoto, Tomoko; Araki, Mikiya; Lin, Yaqiu; Murata, Miho; Takahashi, Ryōsuke; Yamamura, Takashi

doi:10.1212/nxi.0000000000000210

Cited by 31 publications

(22 citation statements)

References 22 publications

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“…This treatment is associated with peripheral sequestration of activated T cells and increased production of proinflammatory cytokines in the blood [8–10]. Inflammatory stimulation decreases PPAR γ promoter activity and gene transcription and PPAR γ agonists are anti-inflammatory and able to upregulate CD36 expression [1, 4, 5].…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, systemic inflammatory activity has been linked to the beneficial effects of NTZ in reducing biomarkers of intrathecal inflammation [8, 9]. It is well accepted that NTZ blocks α 4 β 1 (VLA-4) integrin-mediated leukocyte transmigration to the CNS [8–10]. In this regard, it is interesting that PPAR γ may regulate the expression of β 1 integrin [13].…”

Section: Discussionmentioning

confidence: 99%

“…In this regard, it is of potential relevance that PPAR γ and PPAR α agonists have inhibitory effects on OPN gene expression [17, 18]. The systemic profile of T cells activation and cytokine production induced by NTZ treatment has been shown to be time-dependent and may change differently in single subjects [9, 10]. A major limitation of the present results concerns the small size of the studied population and the short follow-up period of treatment.…”

Section: Discussionmentioning

confidence: 99%

“…In the present exploratory study we analyzed patients treated with Natalizumab (NTZ), a humanized monoclonal antibody against α 4 integrin molecules that inhibits transmigration of leukocytes to the CNS and induces complex alterations of immune functions in peripheral circulation [8–10]. However, the mechanisms underlying the beneficial effects and potential adverse events of this treatment in MS are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

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Natalizumab Treatment Modulates Peroxisome Proliferator-Activated Receptors Expression in Women with Multiple Sclerosis

et al. 2016

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Peroxisome Proliferator-Activated Receptors (PPAR) are transcription factors suggested to be involved in inflammatory lesions of autoimmune encephalomyelitis and multiple sclerosis (MS). Our objective was to assess whether Natalizumab (NTZ) therapy is associated with alterations of PPAR expression in MS patients. We analyzed gene expression of PPAR in peripheral blood mononuclear cells (PBMC) as well as blood inflammatory markers in women with MS previously medicated with first-line immunomodulators (baseline) and after NTZ therapy. No differences in PPARα, PPARβ/δ, PPARγ, and CD36 mRNA expression were found in PBMC between patients under baseline and healthy controls. At three months, NTZ increased PPARβ/δ mRNA (p = 0.009) in comparison to baseline, while mRNA expression of PPARγ and CD36 (a well-known PPAR target gene) was lower in comparison to healthy controls (p = 0.026 and p = 0.028, resp.). Although these trends of alterations remain after six months of therapy, the results were not statistically significant. Osteopontin levels were elevated in patients (p = 0.002) and did not change during the follow-up period of NTZ treatment. These results suggest that PPAR-mediated processes may contribute to the mechanisms of action of NTZ therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Natalizumab Treatment Modulates Peroxisome Proliferator-Activated Receptors Expression in Women with Multiple Sclerosis

et al. 2016

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“…In autoimmune diseases, including an autoimmune model for MS, experimental autoimmune encephalomyelitis (EAE), Th1 and Th17 cells have been associated with organ‐specific and cellular autoimmunities, whereas Th2 cells have been associated with systemic and humoral autoimmunities . Tregs can suppress such autoreactive Th1 and Th17 immune responses . Th1 cells have been shown to suppress Th2 and Th17 cells, and vice versa …”

Section: Tmev‐induced Demyelinating Diseasementioning

confidence: 99%

Three immune‐mediated disease models induced by Theiler's virus: Multiple sclerosis, seizures and myocarditis

Tsunoda

Sato

Omura

et al. 2016

Clinical & Exp Neuroim

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Theiler’s murine encephalomyelitis virus (TMEV) infection has been used as a viral model for multiple sclerosis (MS), as TMEV can induce chronic inflammatory demyelinating lesions with viral persistence in the spinal cord of SJL/J mice. In contrast, when C57BL/6 mice are infected with TMEV, the mice can clear the virus from the central nervous system (CNS), without viral persistence or demyelination, but develop seizures and hippocampal sclerosis, which has been used as a viral model for seizures/epilepsy. In the two TMEV-induced CNS disease models, not only viral infection, but also immune responses contribute to the pathogenesis. Interestingly, acquired immunity plays an effector role in the MS model, whereas innate immunity appears to contribute to the development of seizures. Recently, we have established the third TMEV-induced disease model, a mouse model for viral myocarditis, using C3H mice. TMEV-induced myocarditis is a triphasic disease, which mimics human myocarditis; phase I, mediated by viral replication in the heart and innate immunity; phase II, mediated by acquired immunity; and phase III, resulted from cardiac fibrosis. The genetic susceptibility to the aforementioned three models (MS, seizures and myocarditis) differs among mouse strains. We have compared and contrasted the three models induced by one single pathogen, TMEV, particularly in regard to the roles of T helper cells and natural killer T cells, which will give an insight into how interactions between the immune system and the host’s genetic background determine the tissue tropism of virus and the development of virus-induced organ-specific immunopathology.

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The Molecular Mechanisms Through Which Placental Mesenchymal Stem Cell‐Derived Extracellular Vesicles Promote Myelin Regeneration

et al. 2022

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Multiple sclerosis (MS) is a debilitating degenerative disease characterized by an immunological attack on the myelin sheath leading to demyelination and axon degeneration. Mesenchymal stem/stromal cells (MSCs) and secreted extracellular vesicles (EVs) have become attractive targets as therapies to treat neurodegenerative diseases such as MS due to their potent immunomodulatory and regenerative properties. The placenta is a unique source of MSCs (PMSCs), demonstrates "fetomaternal" tolerance during pregnancy, and serves as a novel source of MSCs for the treatment of neurodegenerative diseases. PMSCs and PMSC-EVs have been shown to promote remyelination in animal models of MS, however, the molecular mechanisms by which modulation of autoimmunity and promotion of myelination occurs have not been well elucidated. The current review will address the molecular mechanisms by which PMSC-EVs can promote remyelination in MS.

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Disrupted balance of T cells under natalizumab treatment in multiple sclerosis

Cited by 31 publications

References 22 publications

Natalizumab Treatment Modulates Peroxisome Proliferator-Activated Receptors Expression in Women with Multiple Sclerosis

Natalizumab Treatment Modulates Peroxisome Proliferator-Activated Receptors Expression in Women with Multiple Sclerosis

Three immune‐mediated disease models induced by Theiler's virus: Multiple sclerosis, seizures and myocarditis

The Molecular Mechanisms Through Which Placental Mesenchymal Stem Cell‐Derived Extracellular Vesicles Promote Myelin Regeneration

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