Contribution of Dysregulated B-Cells and IgE Antibody Responses to Multiple Sclerosis

Seals, Malik R.; Moran, Monica M.; Leavenworth, Jonathan D.; Leavenworth, Jianmei W.

doi:10.3389/fimmu.2022.900117

Cited by 9 publications

(6 citation statements)

References 143 publications

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“…However, it hinders the production of cytotoxicity, which may partly account for the location and function of CD8 + CXCR5 + T cells [40]. Dysregulated humoral immune activation contributes to EAE progression except Th1/Th17-mediated pathogenic mechanisms [11,41].…”

Section: Discussionmentioning

confidence: 99%

Role of follicular CD8+ T cells labeled with B cell helper immunotypes in multiple sclerosis and a murine model

Ding,

Zhang,

Zhao

et al. 2023

Preprint

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Background Multiple sclerosis (MS) has been considered to be a T cell-dependent autoimmune disease of the central nervous system (CNS), and so does the experimental autoimmune encephalomyelitis (EAE) model. Recent studies have revealed a specific subset of CD8 T cells, known as CD8 follicular T cells (CD8+CXCR5+ T), are involved in antiviral, anti-tumor immunity, and systemic autoimmunity. While the role of CD8+CXCR5+ T cells in MS and EAE remains unclear. Methods We detected CD8+CXCR5+ T cell frequency in the peripheral blood of relapsing-remitting MS patients and healthy controls by flow cytometry and analyzed its correlation with disease activity. To show the dynamic changes and locations of CD8+CXCR5+ T cells in secondary lymphoid organs and CNS from EAE mice, flow cytometry and multiplexed immunohistochemistry were performed. RNA-seq, co-culture experiments and in vivo adoptive transfer were then conducted to reveal the phenotypes and functions of CD8+CXCR5+ T cells. Results Expansion of CD8+CXCR5+ T cells in MS patients and EAE mice was detected during the acute phase. In relapsing MS patients, elevated frequencies of circulating CD8+CXCR5+ T cells were positively correlated with new gadolinium-enhancement lesions of CNS. In EAE mice, CD8+CXCR5+ T cells infiltrated in ectopic lymphoid structures of spinal cords and germinal centers of spleens were positively correlated with clinical score and highly expressed ICOS, CD40L, IL-21 and IL-6. In vitro co-culture experiments and CD8+CXCR5+ T-adoptive mice both confirmed the ability of CD8+CXCR5+ T cells to provide B cell help and contribute to disease progression. Conclusions CD8+CXCR5+ T cells which bridged cytotoxic T cells and B cells in MS might be a promising target for developing disease-modifying treatments in the future.

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Section: Discussionmentioning

confidence: 99%

Role of follicular CD8+ T cells labeled with B cell helper immunotypes in multiple sclerosis and a murine model

Ding,

Zhang,

Zhao

et al. 2023

Preprint

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“…These auto-reactive T-lymphocytes are the key drivers of the disease [ 22 ]. However, also abnormally activated glial cells [ 23 , 24 ] and B-lymphocytes play an important role [ 22 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. Long-term depletion of B-lymphocytes by targeting CD20 with monoclonal antibodies can attenuate disease progression in relapsing-remitting but also primary progressive multiple sclerosis [ 32 , 33 , 34 , 35 ], emphasizing the role of different components of the immune system in establishing and maintaining the disease.…”

Section: Primer On Multiple Sclerosis (Ms): Multi-faceted Neuroinflam...mentioning

confidence: 99%

Synapse Dysfunctions in Multiple Sclerosis

Schwarz

Schmitz

2023

IJMS

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Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central nervous system (CNS) affecting nearly three million humans worldwide. In MS, cells of an auto-reactive immune system invade the brain and cause neuroinflammation. Neuroinflammation triggers a complex, multi-faceted harmful process not only in the white matter but also in the grey matter of the brain. In the grey matter, neuroinflammation causes synapse dysfunctions. Synapse dysfunctions in MS occur early and independent from white matter demyelination and are likely correlates of cognitive and mental symptoms in MS. Disturbed synapse/glia interactions and elevated neuroinflammatory signals play a central role. Glutamatergic excitotoxic synapse damage emerges as a major mechanism. We review synapse/glia communication under normal conditions and summarize how this communication becomes malfunctional during neuroinflammation in MS. We discuss mechanisms of how disturbed glia/synapse communication can lead to synapse dysfunctions, signaling dysbalance, and neurodegeneration in MS.

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“…Homology between autoantigens and exogenous allergens leading to cross-reaction of IgE particles, or primary break in self-tolerance leading to the production of IgE autoantibodies are among potential mechanisms of generation of autoreactive IgE ( Charles, 2021 ). IgE directed against autoantigens were observed in a number of autoimmune conditions, including SLE ( Atta et al, 2010 ), BP ( van Beek et al, 2016 ), chronic spontaneous urticaria (CSU) ( Panaszek et al, 2017 ), AITD ( Guo et al, 1997 ), multiple sclerosis ( Seals et al, 2022 ), and mixed connective tissue disease ( Lamri et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Self-reactive IgE and anti-IgE therapy in autoimmune diseases

Olewicz‐Gawlik

Kowala‐Piaskowska

2023

Front. Pharmacol.

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Growing evidence indicates the pathogenic role of autoreactive IgE in autoimmune diseases. Incidence of autoimmune and allergic diseases in the industrialized countries is consistently icreasing, thus leading to concerted efforts to comprehend the regulation of IgE-mediated mechanisms. The first reports of a presence of IgE autoantibodies in patients with autoimmune diseases have been published a long time ago, and it is now recognized that self-reactive IgE can mediate inflammatory response in bullous pemhigoid, systemic lupus erythematosus, chronic urticaria, and atopic dermatitis. The advances in understanding the pathomechanisms of these disorders brought to a successful use of anti-IgE strategies in their management. The present review discusses the current state of knowledge on the IgE-mediated autoimmunity and anti-IgE treatment, and pave the way for further exploration of the subject.

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Contribution of Dysregulated B-Cells and IgE Antibody Responses to Multiple Sclerosis

Cited by 9 publications

References 143 publications

Role of follicular CD8+ T cells labeled with B cell helper immunotypes in multiple sclerosis and a murine model

Role of follicular CD8+ T cells labeled with B cell helper immunotypes in multiple sclerosis and a murine model

Synapse Dysfunctions in Multiple Sclerosis

Self-reactive IgE and anti-IgE therapy in autoimmune diseases

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