Neurons and T cells: Understanding this interaction for inflammatory neurological diseases

Yshii, Lidia; Gebauer, Christina; Bernard‐Valnet, Raphaël; Liblau, Roland

doi:10.1002/eji.201545759

Cited by 27 publications

(16 citation statements)

References 101 publications

(132 reference statements)

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“…Research of the immune system in MS patients has established that MS is an autoimmune disease with T cells, B cells, and probably also autoantibodies as the most important factors contributing to its immunopathogenesis . Autoreactive CD4 + T cells with Th1 (secreting IFN‐γ) or Th1* (secreting IFN‐γ and IL‐17), or those secreting IFN‐γ and GM‐CSF , play an important role in MS, which is partly supported by data from the EAE models .…”

Section: Introduction—ms As An Autoimmune Diseasementioning

confidence: 88%

Current multiple sclerosis treatments have improved our understanding of MS autoimmune pathogenesis

et al. 2016

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Multiple sclerosis (MS) is the most common inflammatory disorder of the central nervous system (CNS) in young adults. When MS is not treated, it leads to irreversible and severe disability. The etiology of MS and its pathogenesis are not fully understood. The recent discovery that MS-associated genetic variants code for molecules related to the function of specific immune cell subsets is consistent with the concept of MS as a prototypic, Tcell-mediated autoimmune disease targeting the CNS. While the therapeutic efficacy of the currently available immunomodulatory therapies further strengthen this concept, differences observed in responses to MS treatment as well as additional clinical and imagingobservations have also shown that the autoimmune pathogenesis underlying MS is much more complex than previously thought. There is therefore an unmet need for continued detailed phenotypic and functional analysis of disease-relevant adaptive immune cells and tissues directly derived from MS patients to unravel the immune etiology of MS in its entire complexity. In this review, we will discuss the currently available MS treatment options and approved drugs, including how they have contributed to the understanding of the immune pathology of this autoimmune disease.Keywords: Autoantibodies r Autoimmune pathogenesis r Autoimmunity r Autoreactive B cells r Autoreactive T cells r Experimental autoimmune encephalomyelitis r Multiple sclerosis r Treatment Introduction-MS as an autoimmune diseaseMS is considered a prototypic organ-specific autoimmune disease targeting the CNS with inflammatory lesions, demyelination, axonal/neuronal damage, and metabolic changes [1,2]. Relapsing-remitting and secondary progressive MS (RRMS, SPMS) are the two most frequent forms of MS, which often affect young adults between 20 and 40 years of age, and women three times more often than men [3]. Typical clinical signs include temporary loss of vision, sensory and motor problems, but also fatigue, neurocognitive changes, and impairment of bladder, bowel, and Correspondence: Britta Engelhardt ; Roland Martin e-mail: bengel@tki.unibe.ch; roland.martin@usz.ch sexual functions. During the relapsing-remitting phase neurological deficits, which occur in bouts and may last from days to a few weeks, usually disappear again, but after several years, disability gradually builds up. Depending on the individual course this secondary progressive disease with continuously increasing disability may never set in, but often starts after 15-20 years of RRMS. In a small percentage of patients such a progressive course is seen from the beginning, which is referred to as primary progressive MS (PPMS) and seen in females and males with equal frequency [3].Evidence for an autoimmune pathogenesis of MS was shown in its animal model, experimental autoimmune encephalomyelitis (EAE) (summarized in [4,5] Treatments of MSAs already noted above, the various treatments of MS deserve particular mentioning not only because they have changed clinical practice and can be considered ...

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Section: Introduction—ms As An Autoimmune Diseasementioning

confidence: 88%

Current multiple sclerosis treatments have improved our understanding of MS autoimmune pathogenesis

et al. 2016

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“…Myelin loss, gliosis , and the resulting axonal pathology culminate in progressive, often severe neurological dysfunction. Emerging data show that the neuroinflammation and neurodegeneration that occur in MS are overlapping and have a complex dependence [8–11] but the autoimmune model of pathogenesis has set early the tone for immunotherapy as the primary clinical management strategy, first by global immune-suppression using aggressive anti-inflammatory drugs, and more recently by selectively targeting specific elements of the immune response [12–15]. The recognition that axonal damage unresponsive to immunotherapy is the main driver of disability in MS has brought the need to emphasize the genetics of grey and white matter cell death and repair as pressing research frontiers in this disease.…”

Section: Ms Is a Genetic Diseasementioning

confidence: 99%

The Genetics of Multiple Sclerosis: From 0 to 200 in 50 Years

2017

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Multiple sclerosis (MS) is a common autoimmune disease that targets myelin in the central nervous system (CNS). Multiple GWAS in the last 10 years have uncovered more than 200 loci that independently contribute to disease pathogenesis. As with many other complex diseases, risk to MS is driven by multiple common variants whose biological effects are not immediately clear. This review will present a historical perspective on the progress made on MS genetics and discuss current work geared towards creating a more complete model that accurately represents the genetic landscape of MS susceptibility. Such a model necessarily includes a better understanding of the individual contributions of each common variant to the cellular phenotypes, and interactions with other genes and with the environment. Future genetic studies in MS will likely focus on the role of rare variants and endophenotypes.

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“…Further, because axons and neurons express MHC-class I, but not class II molecules, damage by CD4þ T cells can only occur by indirect mechanisms or interactions not involving specific antigen recognition, whereas CD8þ T cells can recognize their cognate antigen on neurons/axons and directly damage these. 76,77 Regarding the functional characteristics of autoimmune T cells in MS, older data have emphasized the increase of CD4þ T cells with a T helper 1 (Th1) phenotype based on IFN-γ secretion. 78 Regarding their antigen specificity, it was shown that autoreactive CD4þ T cells with reactivity against major myelin proteins (MBP, PLP, and MOG) are increased, are preferentially Th1 cells, 63 may lose their costimulatory requirements and expression of CD28, 62 and have higher antigen avidity.…”

Section: Immune Mechanisms Involved In the Autoimmune Pathogenesis Ofmentioning

confidence: 99%

Immunology of Multiple Sclerosis

2016

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Multiple sclerosis (MS) is considered a prototypic autoimmune disease of the central nervous system (CNS). A complex genetic background with the HLA-DR15 haplotype as the main genetic risk factor and over 100 mostly immune-related minor risk alleles as well as several environmental factors contribute to the etiology of MS. With respect to pathomechanisms, autoimmune inflammation in early MS is primarily mediated by adaptive immune responses and involves autoreactive T cells, B cells, and antibodies, while the later, chronic stages of MS are characterized by a compartmentalized immune response in the CNS with activated microglia and macrophages. A host of immune cells and mediators can contribute to the autoimmune process, but CNS-related factors such as localization of lesions, vulnerability of oligodendrocytes, neurons/axons, and secondary metabolic changes all play a role in the heterogeneous expression of the disease, including different pathologic lesion patterns, neuroimaging findings, disease courses, and severity and response to treatment.

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Neurons and T cells: Understanding this interaction for inflammatory neurological diseases

Abstract: Central nervous system (CNS) inflammation occurs in a large

Cited by 27 publications

References 101 publications

Current multiple sclerosis treatments have improved our understanding of MS autoimmune pathogenesis

Current multiple sclerosis treatments have improved our understanding of MS autoimmune pathogenesis

The Genetics of Multiple Sclerosis: From 0 to 200 in 50 Years

Immunology of Multiple Sclerosis

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