Interferon-β induces brain-derived neurotrophic factor in peripheral blood mononuclear cells of multiple sclerosis patients

Lalive, Patrice H.; Kantengwa, Salomé; Benkhoucha, Mahdia; Juillard, Catherine; Chofflon, Michel

doi:10.1016/j.jneuroim.2008.04.033

Cited by 39 publications

(39 citation statements)

References 22 publications

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“…However, interferon-β has previously been demonstrated to affect the T regulatory cell compartment [33] and was reported to induce BDNF secretion in immune cells [34,35]. Therefore, we cannot exclude that pleiotropic ‘beneficial’ interferon effects overlay the potential immunological effects of physical activity.…”

Section: Discussionmentioning

confidence: 96%

Physical Activity in Multiple Sclerosis: A Comparative Study of Vitamin D, Brain-Derived Neurotrophic Factor and Regulatory T Cell Populations

Waschbisch

Wenny

Tallner³

et al. 2012

Eur Neurol

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Background: Previous studies suggest beneficial effects of exercise in multiple sclerosis (MS). However, knowledge on the effects of physical activity on the immune system is limited. Objective: To assess potential relationships between cardiorespiratory fitness, cognitive function, and immune parameters in physically active and inactive MS patients. Methods: We identified 83 patients with relapsing-remitting disease, an unrestricted walking range, and stable interferon-β treatment from our data base. Based on the subjective report of physical activity, the lower/inactive (n = 21) and upper/active quartiles (n = 21) of patients were selected. We assessed the frequency of T cells, B cells, NK cells, monocytes and regulatory T cell populations by flow cytometry, measured brain-derived neurotrophic factor and vitamin D serum levels by ELISA, and conducted spiroergometry and transcranial sonography. Results: Physical activity and cardiorespiratory fitness were not associated with brain-derived neurotrophic factor, frequency of T regulatory cells or any other immune cell subpopulation. However, we found a positive correlation of vitamin D serum levels with cardiorespiratory fitness. Conclusion: Overall, we found no negative effect of physical activity on the immune system. The association between vitamin D and cardiorespiratory fitness most likely reflects longer hours of sunlight exposure in active patients, suggesting a desirable ‘side- effect’ of physical activity.

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Section: Discussionmentioning

confidence: 96%

Physical Activity in Multiple Sclerosis: A Comparative Study of Vitamin D, Brain-Derived Neurotrophic Factor and Regulatory T Cell Populations

Waschbisch

Wenny

Tallner³

et al. 2012

Eur Neurol

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“…19 Treatment with IFN␤ has been shown to upregulate expression of BDNF. 20,21 Also, nerve growth factor is induced in a dose-dependent manner by IFN␤ 22 and is inversely correlated to MRI measures of axonal loss. 23 Third, IFN␤-1b induces the expression of proteins associated with the inhibition of oxidative stress.…”

Section: Patientsmentioning

confidence: 99%

Interferon β-1b and glatiramer acetate effects on permanent black hole evolution

et al. 2011

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Objective:To compare interferon ␤-1b (IFN␤-1b) and glatiramer acetate (GA) on new lesion (NL) (gadolinium-enhancing, new T2) evolution into permanent black holes (PBH)-a marker of irreversible tissue damage-in patients with relapsing-remitting multiple sclerosis (RRMS).Methods: BEYOND was a large, phase III, clinical trial comparing IFN␤-1b 250 g, IFN␤-1b 500 g, and GA (2:2:1). Patient scans were reexamined post hoc for PBH in a rater-blinded manner. Two predefined coprimary endpoints compared IFN␤-1b 250 g with GA: first, number of PBH per patient at year 2 evolving from year 1 NL, then proportion of year 1 NL evolving into PBH at year 2. IFN␤-1b 500 g and GA were compared in an exploratory fashion.Results: Approximately 90% (1,957/2,244) of patients had NL at year 1 with follow-up at year 2. Mean numbers of PBH per patient at year 2 evolving from year 1 NL were lower for IFN␤-1b 250 g than GA (0.30 vs 0.43; p ϭ 0.0451). The proportion of NL evolving into PBH was similar (IFN␤-1b 250 g vs GA: 21.6% vs 23.5%; p Ͼ 0.20). For IFN␤-1b 500 g, both the mean PBH number per patient at year 2 evolving from year 1 NL (0.26 vs 0.43; p ϭ 0.0037) and proportion of NL evolving into PBH (16.3% vs 23.5%; p ϭ 0.0409) were lower relative to GA.

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“…Even though CD4 + T-cell autoreactivity has been intensively studied in MS [8][9][10], less is known about the contribution of DCs and B cells to the inflammatory process within the CNS or in the periphery. Once activated in the periphery through APCs, anti-myelin autoreactive T cells cross the bloodbrain barrier, are reactivated by antigenic stimulation, and induce an inflammatory response within the CNS.…”

Section: Introductionmentioning

confidence: 99%

TLR7 signaling exacerbates CNS autoimmunity through downregulation of Foxp3⁺Treg cells

et al. 2013

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The innate Toll-like receptor 7 (TLR7) detects infections by recognizing viral and bacterial single-stranded RNA. In addition to pathogen-derived RNA, immune cells expressing high levels of TLR7, such as B cells and dendritic cells (DCs), can be activated by self-RNA. During myelin-induced experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, TLR7 expression is increased within the central nervous system (CNS). To define the contribution of TLR7 to the development of EAE, we evaluated the course of the disease in C57BL/6-Tlr7-deficient mice compared with that in WT mice and found that TLR7-deficient mice had decreased disease severity. This protection was associated with decreased myelin oligodendrocyte glycoprotein-specific T-cell activation by primed DCs, decreased circulating autoantibodies, attenuated inflammation within the CNS, and increased Foxp3 + regulatory T cells in the periphery and in the CNS. In conclusion, we show that TLR7 is involved in the maintenance of autoimmunity in the pathogenesis of EAE.Keywords: EAE r IL-10 r Multiple sclerosis r TLR7 r Treg cell IntroductionRecognition of microbial components by Toll-like receptors (TLRs) is crucial for host responses against pathogens. While most TLRs are expressed on the cell surface, others such as TLR3, -7, -8, and -9 are expressed intracellularly within endosomal compartments where they detect nucleic acids. Endosomal TLRs recognize viral double-stranded RNA (TLR3), unmethylated CpG DNA Correspondence: Dr. Marie-Laure Santiago-Raber e-mail: marie.santiago@unige.ch (TLR9), and viral single-stranded RNA or synthetic compounds such as imidazoquinolines (TLR7/TLR8) (as reviewed by Kawai and Akira [1]). Previous studies have further provided evidence for the involvement of TLR signaling in the induction of autoantibodies [2,3]. Others studies have implicated TLR7 gene duplication in the pathogenesis of autoimmune diseases such as lupus [4,5]. TLR7 is mainly expressed by B cells but also by dendritic cells (DCs), principally plasmacytoid DCs (pDCs). B cells and pDCs appear to have developed specialized mechanisms for enhancing the delivery of potential ligands to TLR7-and TLR9-containing compartments [6]. In view of the pivotal role of (i) DCs in regulating immunity and tolerance [7], (ii) B cells in the C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2014. 44: 46-57 Cellular immune response 47 adaptive immune response, and (iii) regulatory T (Treg) cells in maintaining T-cell tolerance, we evaluated the importance of DC, B-cell, and Treg-cell activation and generation by ligandbound TLR7 in the framework of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). MS is an immune-mediated disease of the central nervous system (CNS), characterized by the infiltration of inflammatory cells, including autoreactive CD4 + T cells and antigen-presenting cells (APCs), which leads to demyelination and axonal damage [8]. Even though CD4 + T-cell autorea...

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Interferon-β induces brain-derived neurotrophic factor in peripheral blood mononuclear cells of multiple sclerosis patients

Cited by 39 publications

References 22 publications

Physical Activity in Multiple Sclerosis: A Comparative Study of Vitamin D, Brain-Derived Neurotrophic Factor and Regulatory T Cell Populations

Physical Activity in Multiple Sclerosis: A Comparative Study of Vitamin D, Brain-Derived Neurotrophic Factor and Regulatory T Cell Populations

Interferon β-1b and glatiramer acetate effects on permanent black hole evolution

TLR7 signaling exacerbates CNS autoimmunity through downregulation of Foxp3⁺Treg cells

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Interferon-β induces brain-derived neurotrophic factor in peripheral blood mononuclear cells of multiple sclerosis patients

Cited by 39 publications

References 22 publications

Physical Activity in Multiple Sclerosis: A Comparative Study of Vitamin D, Brain-Derived Neurotrophic Factor and Regulatory T Cell Populations

Physical Activity in Multiple Sclerosis: A Comparative Study of Vitamin D, Brain-Derived Neurotrophic Factor and Regulatory T Cell Populations

Interferon β-1b and glatiramer acetate effects on permanent black hole evolution

TLR7 signaling exacerbates CNS autoimmunity through downregulation of Foxp3+Treg cells

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TLR7 signaling exacerbates CNS autoimmunity through downregulation of Foxp3⁺Treg cells