PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “CP: immunology”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

17 recordsLinked to original sources
PubMed2025

Restraint of inflammasome-driven cytokine responses through the mRNA stability protein TTP.

Activation of the NLRP3 inflammasome causes extensive disturbance of cellular homeostasis, with Golgi disruption, mitochondrial dysfunction, and changes in intracellular ion concentration occurring rapidly upon stimulation. Given this, it would seem near certain that these changes might also globally affect cellular signaling pathways, yet few, if any, studies have explored this possibility. Here, we combine genomics and phosphoproteomics to identify inhibition of the ERK1/2 MAP kinase signaling cascade upon inflammasome stimulation. This loss of ERK1/2 activity results in rapid inactivation of the mRNA decay-promoting protein tristetraprolin (TTP), with loss of TTP promoting subsequent increased release of cytokines upon pyroptosis. Further, we observe significantly increased levels of TTP expression in patients with inflammatory bowel disease, a disease for which altered cytokine expression is a key driver of pathogenesis. Inflammasome activation thus rapidly inactivates a pathway designed to suppress cytokine release, potentially exacerbating hyperinflammatory states, including those involved in autoinflammatory disease.

Inflammasomes↗
PubMed2025

Innate immune molecular landscape following controlled human influenza virus infection.

Viral infections can induce prolonged changes in innate immunity. Here, we use blood samples from a human influenza H3N2 challenge study (NCT03883113) to perform comprehensive multi-omics analyses. We detect remodeling of immune programs in circulating innate immune cells that persist after resolution of the infection. We find changes associated with suppressed inflammation, including decreased cytokine and AP-1 gene expression as well as decreased accessibility at AP-1 targets and interleukin-related gene promoter regions. We also find decreased histone deacetylase gene expression, increased MAP kinase gene expression, and increased accessibility at interferon-related gene promoter regions. Genes involved in inflammation and methylation remodeling show modulation of gene-chromatin site regulatory circuit activity. These results reveal a coordinated rewiring of the molecular landscape in innate immune cells induced by mild influenza virus infection.

Humans↗
PubMed2026

Enhanced HIF-1α cooperation by a human RORγt mutant potentiates Th17 pathogenicity.

T helper 17 (Th17) cells are pivotal in mucosal defense and autoimmune pathology, with their function governed by the transcription factor retinoic acid receptor-related orphan receptor gamma t (RORγt). Although genome-wide association studies link RORC variants to inflammatory diseases, their functional consequences remain poorly understood. We identify a pathogenic RORγt mutation N277D (mouse homolog N275D) that amplifies Th17 pathogenicity through cooperation with hypoxia-inducible factor HIF-1α. This mutation enhances IFN-γ and other Th1-type cytokine production by Th17 cells, exacerbating colitis without disrupting T cell development or homeostasis. Integrated transcriptomic and metabolomic profiling reveals activation of glycolytic and hypoxia-associated pathways, consistent with increased RORγtN275D recruitment by HIF-1α to the Pdk1 locus. Notably, silencing Pdk1 normalizes the excessive IFN-γ production in RORγtN275D Th17 cells. Together, these findings define a regulatory axis linking RORγt and HIF-1α that coordinates transcriptional and metabolic programs in pathogenic Th17 cells, providing a framework for dissecting the functional impact of autoimmune risk variants.

CP: immunology↗
PubMed2026

Metadomain and metaloop genome interactions in mammalian T cells.

Recent studies have advanced understanding of chromosomal organization and its role in gene regulation, yet most analyses focus on short-range interactions (<2 Mb), limiting insight into broader architecture. The relationships between topologically associating domains (TADs), sub-TAD loops, cross-TAD interactions, and chromosomal compartmentalization remain poorly understood. Here, using high-resolution Hi-C analysis, we identify extensive multi-megabase and interchromosomal interactions (metaloops) in T lymphocytes that organize into meta-TAD associations (metadomains). These metaloops connect distal promoters and regulatory elements of genes functionally important in T cells, including Ctla4, Ikzf2, Il2ra, Ets1, and Foxo1. Reanalysis of mouse and human datasets confirms their reproducibility and dependence on superenhancers. Genome-wide clustering reveals three distinct interchromosomal hubs, including a superenhancer-enriched hub linked to T cell-specific gene activation. Integrative analysis of regulatory genomics data identifies factors associated with short- versus long-range interactions. This study introduces a broadly applicable computational framework and reveals features of T cell genome organization.

Animals↗
PubMed2026

Spontaneous lytic reactivation drives a persistent B cell-vector pathway for epithelial dissemination of the Epstein-Barr virus.

The Epstein-Barr virus (EBV) establishes lifelong B cell infection via oral transmission; however, it paradoxically drives carcinomas in anatomically distant organs with striking geographic disparities. While genomic studies frequently link specific EBV variants to these epithelial cancers, the mechanisms bridging ubiquitous infection to distant, strain-dependent malignancies remain largely unresolved. Using an induction-free primary B cell system, we identify a circulating B cell-vector pathway driving immortalized epithelial dissemination. We demonstrate that B cells infected with carcinoma-associated strains exhibit markedly higher epithelial transmission compared with those carrying lymphoid strains. This contact-dependent process requires spontaneous lytic reactivation, viral DNA replication, and de novo virion production. Crucially, those infected B cells retain their transmission capacity for months, supporting sustained epithelial seeding. Mechanistically, entry requires gH/gL engagement of EphA2/desmocollin-2 (DSC2), with actin- and PI3K-dependent endocytosis. These findings define a lytic-coupled, receptor-dependent pathway by which the EBV exploits B cells to access the epithelium, offering a mechanistic framework for understanding strain tropism and host-virus interactions.

B cell vector↗
PubMed2025

In vitro protocol demonstrating five functional steps of trained immunity in mice: Implications on biomarker discovery and translational research.

We developed an in vitro methodology to study trained immunity using murine bone-marrow-derived macrophages stimulated with &#x3b2;-glucan and lipopolysaccharide (LPS). Longitudinal analysis of interleukin (IL)-6 and tumor necrosis factor (TNF) production demonstrates that trained macrophages secrete higher cytokine levels following primary stimulation with &#x3b2;-glucan compared to unstimulated macrophages (step 1). After a resting period, trained macrophages return to basal levels of cytokine production (step 2) but rapidly produce enhanced levels of IL-6 and TNF after secondary stimulation with LPS, compared to macrophages individually stimulated with either &#x3b2;-glucan (step 3) or LPS (step 4) alone. The combined cytokine production of macrophages after single stimulation with &#x3b2;-glucan (stimulus 1) and LPS (stimulus 2) is significantly lower than the cytokine levels produced by trained macrophages sequentially stimulated with both &#x3b2;-glucan and LPS (stimulus 1 + 2) (step 5). These results experimentally reproduce the distinctive functional stages that macrophages undergo during the training process.

Animals↗
PubMed2025

The ROR&#x3b3;t ligand-binding domain controls the pathogenicity of IL-17A+ T cells differently in autoimmune diseases of the skin and CNS.

The transcription factor ROR&#x3b3;t orchestrates Th17 lineage differentiation, thymic T cell development, and the pathogenesis of several autoimmune disorders. Lipid ligands are required for appropriate regulation of ROR&#x3b3;t activity, but it is unclear to what extent lipid recognition controls ROR&#x3b3;t function in vivo. Here, we show that the mutation of ROR&#x3b3;t alanine-304 in the ligand-binding domain (LBD) to isoleucine (A304I) abrogates lipid-dependent Th17 differentiation and selectively ameliorates &#x3b3;&#x3b4;T17 cell-mediated psoriatic skin inflammation. In contrast, there is no improvement in experimental autoimmune encephalomyelitis in ROR&#x3b3;tA304I mice. Consistent with this, the expression of genes characteristic of Th17 cells decreases in ROR&#x3b3;tA304I mice, along with a compensatory increase of genes characteristic of Th1-like Th17 cells with pathogenic signatures. Thus, ROR&#x3b3;t alanine-304 in the LBD is indispensable for generating &#x3b3;&#x3b4;T17 and conventional Th17 cells and for the suppression of the Th1-like Th17 pathogenic population, which decouples the pathogenicity of skin and CNS autoimmune diseases.

Animals↗
PubMed2026

Distributed clonal deletion prevents autoimmune disease progression.

Self-reactive B cells arise during development and can increase pathogenicity through activation-induced cytidine deaminase (AID)-mediated diversification. Clonal deletion is thought to eliminate these cells, yet how deletion is distributed across developmental and activation stages to prevent autoimmune disease remains unclear. Here, we show that self-tolerance is enforced through temporally distinct mitochondrial outer membrane permeabilization (MOMP) checkpoints. Using conditional Bcl-2 expression to inhibit MOMP either from B cell development or activation, we find that early inhibition permits survival of autoreactive B cells after peripheral egress, expanding the pool available for activation and AID-dependent diversification. This results in broadened class-switched IgG autoreactivity, complement activation, kidney pathology, and drives lethal autoimmune disease. In contrast, post-activation MOMP inhibition promotes autoreactive cell accumulation and autoantibody production but causes limited tissue damage and normal survival. Together, these findings support a Distributed Clonal Deletion Model in which temporally distinct checkpoints cooperate to constrain autoimmune disease progression.

AID↗
PubMed2026

Humanizing acidic mammalian chitinase variants establish lung immune conditioning and control environmentally driven inflammation and fibrosis.

Chitin, a widespread environmental particle constituent, triggers lung inflammation but is degraded by chitinases. In humans, single-nucleotide polymorphisms (SNPs) in CHIA (acidic mammalian chitinase; AMCase) are associated with lung disease, suggesting that chitinase variants influence responses to airborne particles. Here, we edit the mouse Chia1 locus to generate humanized (hChia) mice harboring common human SNPs. Compared with controls expressing disease-protective SNPs, hChia mice lack robust chitinase activity and fail to degrade natural chitin substrates. Lung-resident lymphocytes and macrophages are spontaneously primed and sensitive to inflammatory triggering by environmental chitin. Immune cell infiltration correlates with airway chitin following challenge, and hChia mice exhibit exacerbated inflammatory and fibrotic lung disease. In humans with acute respiratory failure, alveolar hemorrhage coincides with environmentally derived chitin particles that are susceptible to chitinase degradation, attenuating inflammatory cell responses. Thus, environmental chitin and chitinase activity are crucial determinants of lung immune conditioning with potential therapeutic applications.

AMCase↗
PubMed2026

Selective control of HLA-DRB1 and HLA-DQA1 transcription through DR/DQ super enhancer microelements.

MHC-II gene expression requires promoter-proximal and distal organizing elements. A super enhancer located between the HLA-DR and -DQ genes was dissected into five microdomains (regions A-E) to define its mechanism of action. Regions A and B were required for maximal expression of HLA-DQA1. Region A facilitated HLA-DQA1 expression and substituted for region B in its absence, as well as mediating longer-range interactions with distal CTCF sites. Region D modulated HLA-DRB1 through specific 3D chromatin interactions, whereas a local insulator element (XL9) broadly interacted with the SE. Through deletion of HLA-DRB1 proximal-promoter elements, HLA-DQ expression increased by co-opting interactions with region D, indicating that competition between microelements regulates the absolute levels of MHC-II genes. Together, these data define an additional layer of control for MHC-II genes encoded in one of the most polymorphic and disease-associated regions of the human genome.

CP: immunology↗
PubMed1979

Subcutaneous Corynebacterium parvum in bladder cancer: a controlled study of its immunological effects.

Fourteen out of 26 patients with invasive bladder cancer were randomly assigned to receive weekly subcutaneous injections of Corynebacterium parvum (CP) in addition to standard treatment. Peripheral blood T lymphocyte percentage, K cell activity, mitogen responsiveness, and monocyte and polymorph leucotaxis were measured at intervals over a period of 1 to 2 years. The only consistent difference between the CP-treatment patients and the controls was a slightly higher level of K cell activity in the former, who, however, fared rather worse than the controls in terms of survival.

Cell Survival↗
PubMed1975

Cathodal proteins from primitive (embryonic) red cells of amphibia. Isolation and characterization.

A group of abundant (15% of the soluble protein) nonhemoglobin proteins was isolated from the primitive (embryonic) red cells found in tadpoles, using the cationic properties of the proteins at pH 8.6 to separate them from hemoglobin and other red cell proteins. The cathodal proteins (CP) were resolved into five components, and the two most predominant proteins were separated and characterized. Purified CP-1b and CP-2 had an amino acid composition similar to that of unfractionated cathodal proteins and to each other, except for small variations in the lysine and half-cystine content. The molecular weight of the purified CP-1b and CP-2 was 13 to 14,000, determined by gel filtration chromatography and electrophoresis in the presence of sodium dodecyl sulfate. Cathodal proteins were immunologically related although there were quantitative differences in reactivity. The concentration of cathodal proteins in primitive (embryonic) red cells was 100 times that in definitive (adult) red cells coincided with the replacement of primitive red cells. The synthesis of the cathodal proteins appeared to continue throughout the life of the primitive red cells; when hemoglobin synthesis declined in primitive red cells, approximately half of the protein synthesized by the cells was cathodal protein. Although the function of the cathodal proteins is as yet unknown, the data suggest that the cathodal proteins are a unique characteristic of erythroid differentiation in early development.

Amino Acids↗
PubMed1979

Immunological aspects of cryoprecipitates from the sera of chronic HBsAg carriers.

The sera of chronic hepatitis B surface antigen (HBsAg) carriers and seropositive controls were examined for the presence of immune complexes by cryoprecipitation. Cryoprecipitates (CP) were tested for HBsAg, antibody to HBsAg (anti-HBs), major classes of immunoglobulins, components of the complement system, rheumatoid factor and the ability to activate the alternative pathway of the complement system. For this analysis the methods employed included: radioimmunoassay, reverse passive haemagglutination, immunofluorescence, sucrose density gradient ultracentrifugation, agar-gel diffusion, immunoelectrophoresis, counterimmunoelectrophoresis, latex agglutination, and a haemolytic method for the detection of the activation of the alternative pathway of the complement system. HBsAg was frequently observed in the CP from chronic HBsAg carriers. No anti-HBs activity was detected in the serum of chronic HBsAg carriers. However, the CP from a number of chronic HBsAg carriers contained immunoglobulins and components of the complement system in the absence of rheumatoid factor, anti-HBs activity and were able to activate the alternative pathway of the complement system. On immunoelectrophoresis, a component of the CP reacting with anti-IgG, ANTI-IgA and anti-HBs antisera and demonstrating an altered (faster) electrophoretic mobility was observed. The nature of the CP strongly suggests the presence of circulating immune complexes in asymptomatic chronic HBaAg carriers. These immune complexes may be important in the eventual expression and outcome of clinical disease in apparently healthy carriers of HBsAg.

Adult↗
PubMed1979

Activation of human monocytes by mediators from lymphocytes stimulated with Corynebacterium parvum.

Human monocytes activated in vitro by lymphokine-containing supernatants of autologous or allogeneic lymphocytes stimulated in vitro by Corynebacterium parvum (CP) expressed increased ability to suppress DNA-synthesis in a human tumour cell line. Monocyte activation was not dependent on in vitro differentiation of monocytes, enhanced cytostatic ability being observed at all stages of in vitro differentiation. The lymphokine-induced cytostatic ability was not affected by intensive washing and trypsin treatment of the activated monocytes, but disappeared during 48 hours of in vitro culture of the activated cells. The increased cytostatic ability of lymphokine-activated monocytes did not seem to be due to stable supernatant factors released from monocytes. CP stimulated DNA-synthesis in peripheral blood lymphocytes of 28 normal donors, thus confirming the mitogenic effect of CP on human lymphocytes. Lymphokine production in response to CP correlated with the magnitude of DNA-synthesis, but appeared before DNA-synthesis could be detected in the lymphocytes.

Cell Line↗
PubMed1978

Type-common CP-1 antigen of herpes simplex virus is associated with a 59,000-molecular-weight envelope glycoprotein.

The CP-1 antigen of herpes simplex virus type 1 (HSV-1) is a glycoprotein found in the soluble portion of infected cells, in detergent extracts of infected cell membranes, and in the envelope of purified virus. Antisera were prepared against a further purified form of CP-1 prepared from HSV soluble antigen mix; a glycoprotein, gp52, isolated from detergent-treated infected cells; and detergent extracts of purified virus. Each of the antisera reacted with CP-1 to give a single immunoprecipitin band of identity, and each antiserum neutralized the infectivity of HSV-1 and HSV-2. Our results suggested that the type-common determinants involved in the stimulation of neutralizing antibody resided on a 52,000-molecular-weight (52K) glycoprotein. The envelope of HSV contains several glycoproteins: one component at 59K and a complex of two or three components at 130K, none of which corresponds in molecular weight to gp52. Using the antisera as immunological probes, we performed pulse-chase experiments with [(35)S]methionine-labeled HSV-1-infected cells and followed the disposition of the glycoproteins during the infectious cycle. Each antiserum immunoprecipitated a (35)S-labeled 52K protein from lysates of cells pulse-labeled at 5 h after infection. By 10 h, the label was chased into a 59K protein also precipitable by each of the three antisera. The results suggest that gp52 is a precursor of gp59 and that the latter corresponds in molecular weight to one of the major glycoproteins of the virion envelope.

Antigens, Viral↗