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Project description:Cross-talk between ILC2 and Gata3high Treg locally constrains adaptive type 2 immunity
| PRJNA961816 | ENA
Project description:Innate lymphoid cells (ILC) not only are responsible for shaping the innate immune response but also actively modulate T cell responses. However, the molecular processes regulating ILC-T cell interaction are not yet completely understood. The protein butyrophilin 2a2 (Btn2a2), a co-stimulatory molecule first identified on antigen-presenting cells, has a pivotal role in the maintenance of T cell homeostasis, but the main effector cell and the respective ligands remain elusive. We analyzed the role of Btn2a2 in the ILC-T cell cross talk. We found that the expression of Btn2a2 is upregulated in ILC2 following stimulation with IL-33/IL-25/TSLP. In vitro and in vivo experiments indicated that lack of Btn2a2 expression on ILC2 resulted in elevated T cell responses. We observed an enhanced proliferation of T cells as well as increased secretion of the type 2 cytokines IL-4/IL-5/IL-13 following cocultures with Btn2a2-deficient ILC2. In vivo transfer experiments confirmed the regulatory role of Btn2a2 on ILC2 as Btn2a2-deficient ILC2 induced stronger T cell responses and prevented chronic helminth infections. Taken together, we identified Btn2a2 as a significant player in the regulation of ILC2-T cell interactions.
| S-EPMC8821520 | biostudies-literature
Project description:The ability of tumor cells to evade the immune system is one of the main challenges we confront in the fight against cancer. Multiple strategies have been developed to counteract this situation, including the use of immunostimulant molecules that play a key role in the anti-tumor immune response. Such a response needs to be tumor-specific to cause as little damage as possible to healthy cells and also to track and eliminate disseminated tumor cells. Therefore, the combination of immunostimulant molecules and tumor-associated antigens has been implemented as an anti-tumor therapy strategy to eliminate the main obstacles confronted in conventional therapies. The immunostimulant 4-1BBL belongs to the tumor necrosis factor (TNF) family and it has been widely reported as the most effective member for activating lymphocytes. Hence, we will review the molecular, pre-clinical, and clinical applications in conjunction with tumor-associated antigens in antitumor immunotherapy, as well as the main molecular pathways involved in this association.
| S-EPMC8227424 | biostudies-literature
Project description:Spirochetal diseases such as syphilis, Lyme disease, and leptospirosis are major threats to public health. However, the immunopathogenesis of these diseases has not been fully elucidated. Spirochetes interact with the host through various structural components such as lipopolysaccharides (LPS), surface lipoproteins, and glycolipids. Although spirochetal antigens such as LPS and glycolipids may contribute to the inflammatory response during spirochetal infections, spirochetes such as Treponema pallidum and Borrelia burgdorferi lack LPS. Lipoproteins are most abundant proteins that are expressed in all spirochetes and often determine how spirochetes interact with their environment. Lipoproteins are pro-inflammatory, may regulate responses from both innate and adaptive immunity and enable the spirochetes to adhere to the host or the tick midgut or to evade the immune system. However, most of the spirochetal lipoproteins have unknown function. Herein, the immunomodulatory effects of spirochetal lipoproteins are reviewed and are grouped into two main categories: effects related to immune evasion and effects related to immune activation. Understanding lipoprotein-induced immunomodulation will aid in elucidating innate immunopathogenesis processes and subsequent adaptive mechanisms potentially relevant to spirochetal disease vaccine development and to inflammatory events associated with spirochetal diseases.
| S-EPMC4075078 | biostudies-literature
Project description:Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is a refractory inflammatory disease driven by type 2 immunity, yet the mechanistic link between epithelial stress and immune activation remains elusive. Here, we identify a pathogenic expansion of KRT5⁺KRT15⁺ basal epithelial cells that undergo a metabolic switch to aerobic glycolysis, resulting in lactate overproduction and microenvironment acidification.
2026-01-08 | GSE315521 | GEO
Project description:Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is a refractory inflammatory disease driven by type 2 immunity, yet the mechanistic link between epithelial stress and immune activation remains elusive. Here, we identify a pathogenic expansion of KRT5⁺KRT15⁺ basal epithelial cells that undergo a metabolic switch to aerobic glycolysis, resulting in lactate overproduction and microenvironment acidification. This acidic niche activates the proton-sensing receptor GPR68 on infiltrating CD4⁺ T cells, triggering a Gq–IP1–IKK/ERK signaling cascade that promotes Th2 differentiation and cytokine release. Genetic ablation of GPR68 in CD4⁺ T cells or its pharmacological inhibition with a natural antagonist, 3-Bn-6-Bnid-DKP, ameliorated type 2 inflammation and pathology in vivo. Thus, we define a lactate-GPR68 axis that metabolically couples epithelial dysfunction to adaptive type 2 immunity in ECRSwNP
2025-12-26 | PXD072439 |
Project description:Group 2 innate lymphoid cells (ILC2) have emerged as a major component of type 2 inflammation in mice and humans. ILC2 secrete large amounts of interleukins 5 and 13, which are largely responsible for host protective immunity against helminth parasites because these cytokines induce profound changes in host physiology that include: goblet cell metaplasia, mucus accumulation, smooth muscle hypercontractility, eosinophil and mast cell recruitment, and alternative macrophage activation (M2). This review covers the initial recognition of ILC2 as a distinct cell lineage, the key studies that established their biological importance, particularly in helminth infection, and the new directions that are likely to be the focus of emerging work that further explores this unique cell population in the context of health and disease.
| S-EPMC6539149 | biostudies-literature
Project description:Features of the CRISPR-Cas system, in which bacteria integrate small segments of phage genome (spacers) into their DNA to neutralize future attacks, suggest that its effect is not limited to individual bacteria but may control the fate and structure of whole populations. Emphasizing the population-level impact of the CRISPR-Cas system, recent experiments show that some bacteria regulate CRISPR-associated genes via the quorum sensing (QS) pathway. Here we present a model that shows that from the highly stochastic dynamics of individual spacers under QS control emerges a rank-abundance distribution of spacers that is time invariant, a surprising prediction that we test with dynamic spacer-tracking data from literature. This distribution depends on the state of the competing phage-bacteria population, which due to QS-based regulation may coexist in multiple stable states that vary significantly in their phage-to-bacterium ratio, a widely used ecological measure to characterize microbial systems.
| S-EPMC6094150 | biostudies-literature
Project description:Pathogenic yersiniae utilize a type three secretion system (T3SS) to inject Yop proteins into host cells in order to undermine their immune response. YscM1 and YscM2 proteins have been reported to be functionally equivalent regulators of the T3SS in Yersinia enterocolitica. Here, we show by affinity purification, native gel electrophoresis and small angle x-ray scattering that both YscM1 and YscM2 bind to phosphoenolpyruvate carboxylase (PEPC) of Y. enterocolitica. Under in vitro conditions, YscM1, but not YscM2, was found to inhibit PEPC with an apparent IC(50) of 4 mum (K(i) = 1 mum). To analyze the functional roles of PEPC, YscM1, and YscM2 in Yop-producing bacteria, cultures of Y. enterocolitica wild type and mutants defective in the formation of PEPC, YscM1, or YscM2, respectively, were grown under low calcium conditions in the presence of [U-(13)C(6)]glucose. The isotope compositions of secreted Yop proteins and nine amino acids from cellular proteins were analyzed by mass spectrometry. The data indicate that a considerable fraction of oxaloacetate used as precursor for amino acids was derived from [(13)C(3)]phosphoenolpyruvate by the catalytic action of PEPC in the wild-type strain but not in the PEPC(-) mutant. The data imply that PEPC is critically involved in replenishing the oxaloacetate pool in the citrate cycle under virulence conditions. In the YscM1(-) and YscM2(-) mutants, increased rates of pyruvate formation via glycolysis or the Entner-Doudoroff pathway, of oxaloacetate formation via the citrate cycle, and of amino acid biosynthesis suggest that both regulators trigger the central metabolism of Y. enterocolitica. We propose a "load-and-shoot cycle" model to account for the cross-talk between T3SS and metabolism in pathogenic yersiniae.
| S-EPMC2673285 | biostudies-literature
Project description:The initial steps of spliceosomal small nuclear ribonucleoprotein (snRNP) maturation take place in the cytoplasm. After formation of an Sm-core and a trimethylguanosine (TMG) cap, the RNPs are transported into the nucleus via the import adaptor snurportin1 (SPN) and the import receptor importin-beta. To better understand this process, we identified SPN residues that are required to mediate interactions with TMG caps, importin-beta, and the export receptor, exportin1 (Xpo1/Crm1). Mutation of a single arginine residue within the importin-beta binding domain (IBB) disrupted the interaction with importin-beta, but preserved the ability of SPN to bind Xpo1 or TMG caps. Nuclear transport assays showed that this IBB mutant is deficient for snRNP import but that import can be rescued by addition of purified survival of motor neurons (SMN) protein complexes. Conserved tryptophan residues outside of the IBB are required for TMG binding. However, SPN can be imported into the nucleus without cargo. Interestingly, SPN targets to Cajal bodies when U2 but not U1 snRNPs are imported as cargo. SPN also relocalizes to Cajal bodies upon treatment with leptomycin B. Finally, we uncovered an interaction between the N- and C-terminal domains of SPN, suggesting an autoregulatory function similar to that of importin-alpha.
| S-EPMC1237072 | biostudies-literature