Brain-resident memory T cells represent an autonomous cytotoxic barrier to viral infection.
Journal of Experimental Medicine 213(8):1571 (2016)
Tissue-resident memory T cells (TRM) persist at sites of prior infection and have been shown to enhance pathogen clearance by recruiting circulating immune cells and providing bystander activation. Here, we characterize the functioning of brain-resident memory T cells (bTRM) in an animal model o...
Macroautophagy Proteins Control MHC Class I Levels on Dendritic Cells and Shape Anti-viral CD8(+) T Cell Responses.
Cell Reports 15(5):1076 (2016)
The macroautophagy machinery has been implicated in MHC class II restricted antigen presentation. Here, we report that this machinery assists in the internalization of MHC class I molecules. In the absence of the autophagy factors Atg5 and Atg7, MHC class I surface levels are elevated due to dec...
pDC therapy induces recovery from EAE by recruiting endogenous pDC to sites of CNS inflammation.
Journal of Autoimmunity 67:8 (2016)
Plasmacytoid dendritic cells (pDCs) exhibit both innate and adaptive functions. In particular they are the main source of type I IFNs and directly impact T cell responses through antigen presentation. We have previously demonstrated that during experimental autoimmune encephalomyelitis (EAE) ini...
Neuropathological Techniques to Investigate CNS Pathology in Experimental Autoimmune Encephalomyelitis (EAE).
Methods in Molecular Biology 1304:189 (2016)
Neuropathological techniques such as conventional and immunohistochemical staining of paraffin-embedded tissue sections are instrumental for identification and characterization of aberrations of organ architecture during human inflammatory disorders of the central nervous system (CNS) as in thei...
Reconstruction of single cortical projection neurons reveals primary spine loss in multiple sclerosis.
Brain 139(Pt 1):39 (2016)
Grey matter pathology has emerged as an important contributor to long-term disability in multiple sclerosis. To better understand where and how neuronal damage in the grey matter is initiated, we used high resolution confocal microscopy of Golgi-Cox impregnated tissue sections and reconstructed ...
Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage.
Immunity 43(5):974 (2015)
Tissue damage caused by viral hepatitis is a major cause of morbidity and mortality worldwide. Using a mouse model of viral hepatitis, we identified virus-induced early transcriptional changes in the redox pathways in the liver, including downregulation of superoxide dismutase 1 (Sod1). Sod1(-/-...
IL-27 Induces Th17 Differentiation in the Absence of STAT1 Signaling.
Journal of Immunology 195(9):4144 (2015)
It is known that differentiation of Th17 cells is promoted by activation of STAT3 and inhibited by activation of STAT1. Although both transcription factors are activated by several cytokines, including IL-6, IL-21, and IL-27, each of these cytokines has a very different effect on Th17 differenti...
USP18 lack in microglia causes destructive interferonopathy of the mouse brain.
EMBO Journal 34(12):1612 (2015)
Microglia are tissue macrophages of the central nervous system (CNS) that control tissue homeostasis. Microglia dysregulation is thought to be causal for a group of neuropsychiatric, neurodegenerative and neuroinflammatory diseases, called "microgliopathies". However, how the intracellular stimu...
The methyltransferase Setdb2 mediates virus-induced susceptibility to bacterial superinfection.
Nature Immunology 16(1):67 (2015)
Immune responses are tightly regulated to ensure efficient pathogen clearance while avoiding tissue damage. Here we report that Setdb2 was the only protein lysine methyltransferase induced during infection with influenza virus. Setdb2 expression depended on signaling via type I interferons, and ...
Recurrent multiple CNS hemangioblastomas with VHL disease treated with pazopanib: a case report and literature review.
CNS Oncology 4(6):387 (2015)
Hemangioblastoma is a rare benign neoplasm, accounting for less than 2% of all primitive brain tumors. It may arise sporadically in a solitary form, or associated with Von Hippel-Lindau (VHL) disease with multiple tumors. Surgery is the mainstay treatment, but management is challenging in case o...
Pervasive axonal transport deficits in multiple sclerosis models.
Neuron 84(6):1183 (2014)
Impaired axonal transport can contribute to axon degeneration and has been described in many neurodegenerative diseases. Multiple sclerosis (MS) is a common neuroinflammatory disease, which is characterized by progressive axon degeneration-whether, when, and how axonal transport is affected in t...
Oxysterols promote encephalitogenic CD4 + T cell migration during neuroinflammation
Journal of Neuroimmunology 275(1-2):169 (2014)
Oxysterols are expressed in T lymphocytes and impair type 1 regulatory CD4 T-cell differentiation
Journal of Neuroimmunology 275(1-2):206 (2014)
Hepatocyte growth factor limits autoimmune neuroinflammation via glucocorticoid-induced leucine zipper expression in dendritic cells.
Journal of Immunology 193(6):2743 (2014)
Autoimmune neuroinflammation, including multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), a prototype for T cell-mediated autoimmunity, is believed to result from immune tolerance dysfunction leading to demyelination and substantial neurodegeneration. We p...
Oligodendroglia in cortical multiple sclerosis lesions decrease with disease progression, but regenerate after repeated experimental demyelination.
Acta Neuropathologica 128(2):231 (2014)
Cerebral cortex shows a high endogenous propensity for remyelination. Yet, widespread subpial cortical demyelination (SCD) is a common feature in progressive multiple sclerosis (MS) and can already be found in early MS. In the present study, we compared oligodendroglial loss in SCD in early and ...
Immunological mechanism of action and clinical profile of disease-modifying treatments in multiple sclerosis.
CNS Drugs 28(6):535 (2014)
Multiple sclerosis (MS) is a life-long, potentially debilitating disease of the central nervous system (CNS). MS is considered to be an immune-mediated disease, and the presence of autoreactive peripheral lymphocytes in CNS compartments is believed to be critical in the process of demyelination ...
Myelin membrane wrapping of CNS axons by PI(3,4,5)P3-dependent polarized growth at the inner tongue.
Cell 156(1-2):277 (2014)
Central nervous system myelin is a multilayered membrane sheath generated by oligodendrocytes for rapid impulse propagation. However, the underlying mechanisms of myelin wrapping have remained unclear. Using an integrative approach of live imaging, electron microscopy, and genetics, we show that...
TLR7 signaling exacerbates CNS autoimmunity through downregulation of Foxp3+ Treg cells.
European Journal of Immunology 44(1):46 (2014)
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 exper...
Neuroprotective intervention by interferon-γ blockade prevents CD8+ T cell-mediated dendrite and synapse loss.
Journal of Experimental Medicine 210(10):2087 (2013)
Neurons are postmitotic and thus irreplaceable cells of the central nervous system (CNS). Accordingly, CNS inflammation with resulting neuronal damage can have devastating consequences. We investigated molecular mediators and structural consequences of CD8(+) T lymphocyte (CTL) attack on neurons...
Magnetic resonance imaging reveals therapeutic effects of interferon-beta on cytokine-induced reactivation of rat model of multiple sclerosis.
Journal of Cerebral Blood Flow and Metabolism 33(5):744 (2013)
Interferon-β (IFN-β) drugs are considered to derive their beneficial effects on multiple sclerosis (MS) progression via their antiinflammatory properties, but the precise mechanism of action remains unclear. Here, we sought to discover how IFN-β impacts on inflammation-associated aggravation of ...