Toll-Like Receptor Signaling and Its Role in Cell-Mediated Immunity

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: March 3, 2022

Innate immunity is the first defense system against invading pathogens. Toll-like receptors (TLRs) are well-defined pattern recognition responsible for pathogen and induction of innate immune responses. Since their discovery, TLRs have revolutionized field immunology by filling gap between initial pathogens cells activation adaptive response. critically link to regulating antigen-presenting key cytokines. Furthermore, recent studies also shown that TLR signaling can directly regulate T cell activation, growth, differentiation, development, function under diverse physiological conditions. This review provides an overview pathways regulators discusses how signaling, indirectly, regulates cell-mediated immunity. In addition, we discuss important in host’s infectious diseases, autoimmune cancer.

Language: Английский

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An Overview of Systemic Lupus Erythematosus (SLE) Pathogenesis, Classification, and Management

Cureus, Journal Year: 2022, Volume and Issue: unknown

Published: Oct. 15, 2022

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multisystem involvement. It multifactorial and involves epigenetic, genetic, ecological, environmental factors. Primarily it leads to activation of both innate adaptive immunity, which consequently autoreactive B cell by T cells immune complexes deposition in tissues leading an cascade that may be limited the single organ or can cause widespread systemic SLE heterogeneous presentation, broad spectrum clinical manifestations ranging from clinically mild self-resolving symptoms severe life-threatening Clinical serological heterogeneity are critical features SLE, posing significant challenge its diagnosis. Antinuclear antibodies (ANA) telltale marker more than 95% patients. The improved set European Alliance Associations for Rheumatology (EULAR) classification enabled accurate diagnosis SLE. treatment focuses on remission, preventing damage, improving overall quality life.

Language: Английский

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Toll‐like receptors in health and disease

MedComm, Journal Year: 2024, Volume and Issue: 5(5)

Published: April 29, 2024

Toll-like receptors (TLRs) are inflammatory triggers and belong to a family of pattern recognition (PRRs) that central the regulation host protective adaptive immune responses. Activation TLRs in innate myeloid cells directs lymphocytes produce most appropriate effector responses eliminate infection maintain homeostasis body's internal environment. Inappropriate TLR stimulation can lead development general autoimmune diseases as well chronic acute inflammation, even cancer. Therefore, expected be targets for therapeutic treatment inflammation-related diseases, microbial infections, human cancers. This review summarizes recent discoveries molecular structural biology TLRs. The role different signaling pathways such diabetes, cardiovascular respiratory digestive cancers (oral, gastric, breast, colorectal) is highlighted new drugs related clinical treatments trials, providing an overview potential prospects TLR-related diseases.

Language: Английский

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B-cell depletion in autoimmune diseases

Annals of the Rheumatic Diseases, Journal Year: 2024, Volume and Issue: unknown, P. ard - 225727

Published: May 22, 2024

B cells have a pivotal function in the pathogenesis of autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus. In disease, orchestrate antigen presentation, cytokine production autoantibody production, latter via their differentiation into antibody-secreting plasmablasts plasma cells. This article addresses current therapeutic strategies to deplete order ameliorate or potentially even cure disease. It main target antigens B-cell lineage that are used for approaches. Furthermore, it summarises evidence successful treatment disease with monoclonal antibodies targeting limitations challenges these Finally, concept deep depletion immunological reset by chimeric receptor T is discussed, well lessons from this approach better understanding role

Language: Английский

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Selective CAR-T cell mediated B cell depletion suppresses interferon signature in SLE

JCI Insight, Journal Year: 2024, Volume and Issue: 9(12)

Published: May 9, 2024

Applying advanced molecular profiling together with highly specific targeted therapies offers the possibility to better dissect mechanisms underlying immune-mediated inflammatory diseases such as systemic lupus erythematosus (SLE) in humans. Here we apply a combination of single-cell RNA-Seq and T/B cell repertoire analysis perform an in-depth characterization changes immune-signature upon CD19 CAR T cell-mediated depletion B cells patients SLE. The resulting data sets not only confirm selective reset response but simultaneously reveal consequent transcriptional signature monocyte subsets that respond profound reduction type I IFN signaling. Our current data, thus, provide evidence for causal relationship between increased observed SLE additionally demonstrate usefulness combining analytic approaches decipher

Language: Английский

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The TLR7/9 adaptors TASL and TASL2 mediate IRF5-dependent antiviral responses and autoimmunity in mouse

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 24, 2025

Abstract Endosomal nucleic acid sensing by Toll-like receptors (TLRs) is central to antimicrobial immunity and several autoimmune conditions such as systemic lupus erythematosus (SLE). The innate immune adaptor TASL mediates, via the interaction with SLC15A4, activation of IRF5 downstream human TLR7, TLR8 TLR9, but pathophysiological functions this axis remain unexplored. Here we show that SLC15A4 deficiency results in a selective block TLR7/9-induced activation, while loss leads strong incomplete impairment, which depends on cell type TLR engaged. This residual activity ascribed previously uncharacterized paralogue, Gm6377 , named here TASL2. Double knockout TASL2 (TASL DKO ) phenocopies SLC15A4-deficient feeble mice showing comparable impairment humoral responses. Consequently, fail control chronic LCMV infection, being protected pristane-induced SLE disease model. Our study thus demonstrates critical role TASL/TASL2 for TLR7/9-driven inflammatory responses, further supporting therapeutic potential targeting complex related diseases.

Language: Английский

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Translocating gut pathobiont Enterococcus gallinarum induces T _H 17 and IgG3 anti-RNA–directed autoimmunity in mouse and human

Science Translational Medicine, Journal Year: 2025, Volume and Issue: 17(784)

Published: Feb. 5, 2025

Chronic autoimmune diseases often lead to long-term sequelae and require lifelong immunosuppression because of an incomplete understanding the triggers drivers in genetically predisposed patients. Gut bacteria that escape gut barrier, known as translocating pathobionts, have been implicated instigators perpetuators extraintestinal mice. The microbial contributions autoimmunity humans remain largely unclear, including whether specific pathological human adaptive immune responses are triggered by such pathobionts. Here, we show pathobiont Enterococcus gallinarum can induce both mouse interferon-γ + T helper 17 (T H 17) differentiation immunoglobulin G3 (IgG3) subclass switch anti– E. RNA antibodies, which correlated with anti-human autoantibody patients systemic lupus erythematosus (SLE) hepatitis, two diseases. RNA, but not Toll-like receptor 8 (TLR8), TLR8-mediated monocyte activation promoted induction . Translocation increased anti-RNA titers renal pathophysiology murine gnotobiotic models disease activity SLE. These studies elucidate cellular mechanisms how a induces cell– B cell–dependent provide framework for developing host- microbiota-derived biomarkers targeted therapies

Language: Английский

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Molecular mechanisms controlling age‐associated B cells in autoimmunity*

Immunological Reviews, Journal Year: 2022, Volume and Issue: 307(1), P. 79 - 100

Published: Jan. 31, 2022

Abstract Age‐associated B cells (ABCs) have emerged as critical components of immune responses. Their inappropriate expansion and differentiation increasingly been linked to the pathogenesis autoimmune disorders, aging‐associated diseases, infections. ABCs exhibit a distinctive phenotype and, in addition classical cell markers, often express transcription factor T‐bet myeloid markers like CD11c; hence, these are also commonly known CD11c + cells. Formation is promoted by combinations innate adaptive signals. In producing antibodies, display antigen‐presenting proinflammatory capabilities. It becoming appreciated that ABC compartment exhibits high degree heterogeneity, plasticity, sex‐specific regulation can differentiate into effector progeny via several routes particularly settings. this review, we will discuss initial insights obtained on molecular machinery controls highlight some unique aspects control system may enable fulfill their role Given expanding array disorders pathophysiological settings which being implicated, deeper understanding could important broad therapeutic implications for successful, albeit daunting, task targeting

Language: Английский

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Lipid Metabolism: Immune Regulation and Therapeutic Prospectives in Systemic Lupus Erythematosus

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: March 18, 2022

Systemic lupus erythematosus (SLE) is a heterogeneous disease characterized by the production of abnormal autoantibodies and immune complexes that can affect organ systems, particularly kidneys cardiovascular system. Emerging evidence suggests dysregulated lipid metabolism, especially in key effector cells, such as T B innate exerts complex effects on pathogenesis progression SLE. Beyond their important roles membrane components energy storage, different lipids also modulate cellular processes, proliferation, differentiation, survival. In this review, we summarize altered metabolism associated mechanisms involved Furthermore, discuss recent progress role potential therapeutic target

Language: Английский

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The X in seX-biased immunity and autoimmune rheumatic disease

The Journal of Experimental Medicine, Journal Year: 2022, Volume and Issue: 219(6)

Published: May 5, 2022

Sexual dimorphism in the composition and function of human immune system has important clinical implications, as males females differ their susceptibility to infectious diseases, cancers, especially systemic autoimmune rheumatic diseases. Both sex hormones X chromosome, which bears a number immune-related genes, play critical roles establishing molecular basis for observed differences dysfunction. Here, we review our current understanding health disease, with specific focus on contribution chromosome striking female bias three

Language: Английский

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