Design, synthesis, in vitro and in vivo biological evaluation of pterostilbene derivatives for anti-inflammation therapy

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 39(1)

Published: Feb. 29, 2024

Pterostilbene (PST) is a naturally derived stilbene compound in grapes, blueberries, and other fruits. It also natural dietary with wide range of biological activities such as antioxidant, anti-inflammatory, antitumor, so on. Structural modifications based on the chemical scaffold pterostilbene skeleton are great importance for drug discovery. In this study, skeletons were used to design novel anti-inflammatory compounds high activity low toxicity. A total 30 new found synthesised, their safety screened. Among them, E2 was most active (against NO: IC50 = 0.7 μM) than celecoxib. Further studies showed that exerted by blocking LPS-induced NF-κB/MAPK signalling pathway activation. vivo experiments revealed had good alleviating effect acute colitis mice. conclusion, may be promising lead compound.

Language: Английский

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Beyond classical immunity: Mast cells as signal converters between tissues and neurons

Immunity, Journal Year: 2024, Volume and Issue: 57(12), P. 2723 - 2736

Published: Dec. 1, 2024

Language: Английский

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The origins and longevity of IgE responses as indicated by serological and cellular studies in mice and humans

Allergy, Journal Year: 2023, Volume and Issue: 78(12), P. 3103 - 3117

Published: July 7, 2023

The existence of long-lived IgE antibody-secreting cells (ASC) is contentious, with the maintenance sensitization by continuous differentiation short-lived

Language: Английский

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How type‐2 dendritic cells induce Th2 differentiation: Instruction, repression, or fostering T cell‐T cell communication?

Allergy, Journal Year: 2024, Volume and Issue: 80(2), P. 395 - 407

Published: Sept. 26, 2024

Allergic disease is caused by the activation of allergen-specific CD4+ type-2 T follicular helper cells (Tfh2) and 2 (Th2) effector that secrete cytokines IL-4, IL-5, IL-9, IL-13 upon allergen encounter, thereby inducing IgE production B tissue inflammation. While it accepted priming differentiation naïve into Th2 requires presentation type dendritic (DC2s), underlying signals remain unidentified. In this review we focus on interaction between allergen-presenting DC2s in lymph node (LN), potential mechanisms which might instruct differentiation. We outline recent advances characterizing DC2 development heterogeneity. sensing current proposed differentiation, with specific consideration role how they contribute to each mechanism. Finally, assess publications reporting a detailed analysis DC-T cell interactions LNs support Together, these studies are starting shape our understanding key initial step allergic immune response.

Language: Английский

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IL-21 promotes plasmablast differentiation independent of proliferation in vitro

Immunology Letters, Journal Year: 2025, Volume and Issue: 273, P. 106980 - 106980

Published: Feb. 7, 2025

Language: Английский

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Maternal IgE Influence on Fetal and Infant Health

Immunological Reviews, Journal Year: 2025, Volume and Issue: 331(1)

Published: April 25, 2025

ABSTRACT Immunoglobulin E (IgE) is the most recently discovered and evolved mammalian antibody type, best known for interacting with mast cells (MCs) as immune effectors. IgE‐mediated antigen sensing by MC provides protection from parasites, venomous animals, bacteria, other insults to barrier tissues exposed environment. IgE MCs act inflammation amplifiers response adjuvants. Thus, production memory formation are greatly constrained require specific licensing. Failure of regulation gives rise allergic disease, one top causes chronic illness. Increasing evidence suggests allergy development often starts early in life, including prenatally, maternal influence being central shaping offspring's system. Although exists before birth, an endogenous source IgE‐producing B has not been identified. This review discusses mechanisms transfer into offspring, its interactions offspring antigen‐presenting cells, consequences allergen sensitization development. We discuss multifaceted effects pre‐existing IgG, IgE, their glycosylation on functionality progeny. Understanding predisposing life may allow targeting existing therapeutics guide new ones.

Language: Английский

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IgE in the Regulation of Adaptive Immune Responses

Immunological Reviews, Journal Year: 2025, Volume and Issue: 331(1)

Published: May 1, 2025

ABSTRACT Immunoglobulin E (IgE) plays a dual role in the immune system, providing protection against pathogens while also mediating pathological hypersensitivity reactions. Its function is mainly studied context of immediate inflammatory responses, where IgE‐sensitized effector cells, such as mast cells and basophils, are triggered by cross‐linking antigen. An often‐overlooked feature IgE biology its strong ability to boost secondary adaptive thus acting physiological adjuvant. The regulation these responses influenced various factors, including primary Ig structure, post‐translational modifications glycosylations, structural properties antigens, interaction with receptors. Interestingly, not only generates antigen‐specific but IgE‐specific autoimmune responses. Natural IgG anti‐IgE autoantibodies circulate at surprisingly high levels, even healthy individuals, contributing serum levels Understanding emerging concepts, beyond singular focus on initial production cell activation, could contribute better understanding immunological functions IgE. In this review, we aim provide an overview current knowledge immunogenicity. Many open questions remain negative positive feedback mechanisms which regulates response, hope inspire future research into underlying IgE‐regulated their potential implications for therapeutic strategies diseases.

Language: Английский

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IL‐1R2 Expression in Tfr Cells Controls Allergic Anaphylaxis by Regulating IgG Versus IgE Responses

Allergy, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 18, 2024

The antibody response is regulated by follicular T helper (Tfh) and regulatory (Tfr) cells that control the germinal center (GC) reaction [1]. We previously showed Tfh express IL-1 receptor IL-1R1, while Tfr decoy IL-1R2 IL-1R1. In contrast, (Tregs) largely do not IL-1Rs [2]. role of expressed in regulation allergy poorly understood. recently generated a mouse line which knocked out FoxP3+ (FoxP3creIL-1R2lox mice) [3]. Here, we compared these mice to their FoxP3cre controls model ovalbumin (OVA) sensitization anaphylaxis. Compared mice, FoxP3creIL-1R2lox displayed strong exacerbation allergic anaphylaxis characterized increased total IgE levels, blood basophil-displayed surface density, significantly enhanced systemic OVA challenge (Figure 1A–D, Figure S1A–D). Moreover, vitro OVA-challenged basophils derived from degranulation controls, demonstrating an increase reactive 1E–G, S1F). contrast this response, reduced OVA-specific IgG responses, including IgG1 IgG2b subclasses 1H–J). Blockade inhibitory FcγRIIb worsened but had no effect FoxP3creIL-1R2lox, suggesting IgG-dependent protection occurs 1 K). vitro, only serum FcγR-dependent binding IgG-OVA complexes inhibited basophil via 1L,M, S1G,H). Thus, driven reduction protective IgG. next investigated splenic GC response. overall elevated cell numbers, IL-4+Tfh cells. However, even more, resulting Tfr:Tfh ratios 2A–C, S3). Looking at B-cell subsets, noted plasmablasts (PB), whereas Bcell (GCB) numbers were 2D). Interestingly, GCB levels proliferation apoptosis, activity 2E,F, with notion, 2G). Finally, isolated splenocytes re-stimulated IL-1β and/or OVA. observed IL-1R1-dependent activation IL-1R2-deleted cells, upon re-stimulation did occur 2H–K, S4). These results extend our previous report showing deletion enhances own agreement findings Tregs IL-1Rs, those proliferate S4K) A recent study cellular responses antibodies immunization through increasing [4]. study, observe immunization. translated supressed. differences could be explained here-observed increases different approach. Future studies will resolve further detail. propose expansion, ratios, may suppress maturation GCs favoring responses. quality sufficient raise specific potentially leads IgG:IgE drives toward 2L). Our are supported fact arises distinct pathway IgG, can independent GCs. switching PB formation directly IgM, or post-GC precursors [5, 6]. fit both scenarios, though latter would require initially during sensitization. Overall, questions difficult answer as long details itself remain unclear. summary, show level expression regulate between versus pathways for thus controlling D.K. conceptualized supervised study. Methodologies developed P.E., A.B., G.F., H.D.L., B.B., S.G.D., Experiments conducted R.V., G.F. Visualization was handled P.E. Funding acquired original draft written edited D.K., before final review all authors. thank animal facility team Doriane Foret, Flora Issert, Kim Nguyen, Olivier Bregerie support. authors declare conflicts interest. data support available corresponding author reasonable request. Data S1. S2. Please note: publisher responsible content functionality any supporting information supplied Any queries (other than missing content) should directed article.

Language: Английский

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The trajectory of human B‐cell function, immune deficiency, and allergy revealed by inborn errors of immunity

Immunological Reviews, Journal Year: 2023, Volume and Issue: 322(1), P. 212 - 232

Published: Nov. 20, 2023

Summary The essential role of B cells is to produce protective immunoglobulins (Ig) that recognize, neutralize, and clear invading pathogens. This results from the integration signals provided by pathogens or vaccines stimulatory microenvironment within sites immune activation, such as secondary lymphoid tissues, drive mature differentiate into memory antibody (Ab)‐secreting plasma cells. In this context, undergo several molecular events including Ig class switching somatic hypermutation in production high‐affinity Ag‐specific Abs different classes, enabling effective pathogen neutralization long‐lived humoral immunity. However, perturbations these key signaling pathways underpin dyscrasias deficiency autoimmunity allergy. Inborn errors immunity disrupt critical have identified non‐redundant requirements for eliciting maintaining but concomitantly prevent dysregulation. Here, we will discuss our studies on human cells, how investigation cytokine fundamental B‐cell formation, Ab well regulating context versus allergic responses.

Language: Английский

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Revisiting immunity versus exposure in schistosomiasis: A mathematical modelling study of delayed concomitant immunity

PNAS Nexus, Journal Year: 2024, Volume and Issue: 3(10)

Published: Oct. 1, 2024

Abstract The relative contributions of exposure vs. acquired immunity to the epidemiology human schistosomiasis has been long debated. While there is considerable evidence that humans acquire partial infection, age- and sex-related contact patterns with water bodies contaminated infectious cercarial schistosome larvae also contribute typical epidemiological profiles infection. Here, we develop a novel transmission model incorporates both partially protective “delayed concomitant” immunity—stimulated by dying worms—and host sex-dependent exposure. We use contemporary Bayesian approach fit historical individual data on cercaria, eggs per gram feces, immunoglobulin E antibodies specific Schistosoma mansoni Tegumental-Allergen-Like protein 1 collected from highly endemic community in Uganda, estimating immunity. find variants incorporating or omitting delayed concomitant describe equally well sex-specific immunoepidemiological observed before intervention 18 months after treatment. Over longer time horizons, creates subtle differences during routine mass drug administration may confer resilience against elimination. discuss our findings broader context immunoepidemiology schistosomiasis.

Language: Английский

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