Molecular mimicry and autoimmunity

Journal of Autoimmunity, Journal Year: 2018, Volume and Issue: 95, P. 100 - 123

Published: Oct. 26, 2018

Molecular mimicry is one of the leading mechanisms by which infectious or chemical agents may induce autoimmunity. It occurs when similarities between foreign and self-peptides favor an activation autoreactive T B cells a foreign-derived antigen in susceptible individual. However, molecular unlikely to be only underlying mechanism for autoimmune responses; other factors such as breach central tolerance, non-specific bystander activation, persistent antigenic stimuli (amongst others) also contribute development diseases. Host genetics, exposure microbiota environmental chemicals are additional links our understanding mimicry. Our current knowledge detailed limited issues prolonged periods latency before appearance disease, lack enough statistical power epidemiological studies, limitations potential role genetics human relevance inbred murine models diverse population especially technology systematically dissect T-cell repertoire B-cell responses. Nevertheless, studies on T-cells that generated secondary mimicry, diversity receptor repertoires auto-reactive T-cells, cryptic antigens, generation responses, interaction adjuvants with host immune systems all provide clues advancing involved evolving concept potentially aid prevention treatment

Language: Английский

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Reassessing B cell contributions in multiple sclerosis

Nature Immunology, Journal Year: 2018, Volume and Issue: 19(7), P. 696 - 707

Published: June 14, 2018

Language: Английский

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Targeting metabolism to regulate immune responses in autoimmunity and cancer

Nature Reviews Drug Discovery, Journal Year: 2019, Volume and Issue: 18(9), P. 669 - 688

Published: July 30, 2019

Language: Английский

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V(D)J recombination, somatic hypermutation and class switch recombination of immunoglobulins: mechanism and regulation

Immunology, Journal Year: 2020, Volume and Issue: 160(3), P. 233 - 247

Published: Feb. 7, 2020

Immunoglobulins emerging from B lymphocytes and capable of recognizing almost all kinds antigens owing to the extreme diversity their antigen-binding portions, known as variable (V) regions, play an important role in immune responses. The exons encoding V regions are (variable), D (diversity), or J (joining) genes. V, D, segments exist multiple copy arrays on chromosome. recombination V(D)J gene is key mechanism produce antibody diversity. recombinational process, including randomly choosing a pair segments, introducing double-strand breaks adjacent each segment, deleting (or inverting some cases) intervening DNA ligating together, defined recombination, which contributes surprising immunoglobulin vertebrate systems. To enhance both ability immunoglobulins recognize bind foreign effector capacities expressed antibodies, naive cells will undergo class switching (CSR) somatic hypermutation (SHM). However, genetics mechanisms CSR SHM not clear. In this review, we summarize major progress studies well SHM, regulatory mechanisms.

Language: Английский

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Recent Advances in Understanding the Pathogenesis of Rheumatoid Arthritis: New Treatment Strategies

Cells, Journal Year: 2021, Volume and Issue: 10(11), P. 3017 - 3017

Published: Nov. 4, 2021

Rheumatoid arthritis (RA) is considered a chronic systemic, multi-factorial, inflammatory, and progressive autoimmune disease affecting many people worldwide. While patients show very individual courses of disease, with RA focusing on the musculoskeletal system, joints are often severely affected, leading to local inflammation, cartilage destruction, bone erosion. To prevent joint damage physical disability as one symptoms RA, early diagnosis critical. Auto-antibodies play pivotal clinical role in systemic RA. As biomarkers, they could help make more efficient diagnosis, prognosis, treatment decision. Besides auto-antibodies, several other factors involved progression such epigenetic alterations, post-translational modifications, glycosylation, autophagy, T-cells. Understanding interplay between these would contribute deeper insight into causes, mechanisms, progression, disease. In this review, latest research findings discussed better understand pathogenesis, finally, strategies for therapy presented, including both conventional approaches new methods that have been developed recent years or currently under investigation.

Language: Английский

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The Therapeutic and Pathogenic Role of Autophagy in Autoimmune Diseases

Frontiers in Immunology, Journal Year: 2018, Volume and Issue: 9

Published: July 31, 2018

Autophagy is a complicated cellular mechanism that maintains and tissue homeostasis integrity via degradation of senescent, defective subcellular organelles, infectious agents, misfolded proteins. Accumulating evidence has shown autophagy involved in numerous immune processes, such as removal intracellular bacteria, cytokine production, autoantigen presentation, survival lymphocytes, indicating an apparent important role innate adaptive responses. Indeed, genome-wide association studies (GWAS), autophagy-related gene polymorphisms have been suggested to be associated with the pathogenesis several autoimmune inflammatory disorders, systemic lupus erythematosus (SLE), psoriasis, rheumatoid arthritis (RA), bowel disease (IBD) multiple sclerosis (MS). In addition, conditional knockdown genes mice displayed therapeutic effects on models by reducing levels cytokines autoreactive cells. However, inhibition accelerates progress some diseases promotion production. Therefore, this review will summarize current knowledge regulation discuss pathogenic broaden our understanding etiopathogenesis shed light autophagy-mediated therapies.

Language: Английский

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Control of Early B Cell Development by the RNA N6-Methyladenosine Methylation

Cell Reports, Journal Year: 2020, Volume and Issue: 31(13), P. 107819 - 107819

Published: June 1, 2020

The RNA N6-methyladenosine (m6A) methylation is installed by the METTL3-METTL14 methyltransferase complex. This modification has critical regulatory roles in various biological processes. Here, we report that deletion of Mettl14 dramatically reduces mRNA m6A developing B cells and severely blocks cell development mice. Deletion impairs interleukin-7 (IL-7)-induced pro-B proliferation large-pre-B-to-small-pre-B transition causes dramatic abnormalities gene expression programs important for development. Suppression a group transcripts cytoplasmic reader YTHDF2 to IL-7-induced proliferation. In contrast, block independent YTHDF1 or but associated with failure properly upregulate key transcription factors regulating this transition. Our data highlight its proteins early

Language: Английский

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IL-10-producing regulatory B cells restrain the T follicular helper cell response in primary Sjögren’s syndrome

Cellular and Molecular Immunology, Journal Year: 2019, Volume and Issue: 16(12), P. 921 - 931

Published: April 4, 2019

Language: Английский

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Human B-1 Cells and B-1 Cell Antibodies Change With Advancing Age

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: March 19, 2019

Age-related deficits in the immune system have been associated with an increased incidence of infections, autoimmune diseases and cancer. Human B cell populations change quantitatively qualitatively elderly. However, function human B-1 cells, which play critical anti-microbial housekeeping roles, not studied older age population. In present work, we analyzed how frequency, repertoire peripheral blood cells (CD19+CD20+CD27+ CD38low/intCD43+) age. Our results show that only percentage but also their ability to spontaneously secrete IgM decreased Further, expression levels transcription factors XBP-1 Blimp-1 were significantly lower, while PAX-5, characteristic non-secreting was higher, healthy donors over 65 years (old) as compared between 20-45 (young). To further characterize population individuals, performed single sequencing analysis heavy chains from young old donors. We found reduced diversity antibodies well differences usage certain VH DH specific genes, younger. Overall, our impairment advancing age, might impact quality life onset disease within elderly

Language: Английский

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Multiple Functions of B Cells in the Pathogenesis of Systemic Lupus Erythematosus

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(23), P. 6021 - 6021

Published: Nov. 29, 2019

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by excessive autoantibody production and multi-organ involvement. Although the etiology of SLE still remains unclear, recent studies have several pathogenic B cell subsets regulatory involved in pathogenesis SLE. Among subsets, age-associated cells (ABCs) are a newly identified subset autoreactive with T-bet-dependent transcriptional programs unique functional features Accumulation T-bet+ CD11c+ ABCs has been observed patients mouse models. In addition, innate-like receptor (BCR) expression long-lived plasma persistent contribute to development Moreover, immune suppressive functions identified, while impaired inhibitory effects indicated Thus, further elucidation on will provide new insights understanding lead novel therapeutic interventions treatment

Language: Английский

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