PIM1 signaling in immunoinflammatory diseases: an emerging therapeutic target DOI Creative Commons
Xue Yang, Chunming Liu, Yuxi Lei

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 20, 2024

PIM1, the proviral integration site for Moloney murine leukemia virus, is a member of serine/threonine protein kinase family. It involved in many biological events, such as cell survival, cycle progression, proliferation, and migration, has been widely studied malignant diseases. However, recent studies have shown that PIM1 plays prominent role immunoinflammatory diseases, including autoimmune uveitis, inflammatory bowel disease, asthma, rheumatoid arthritis. can function signal transduction by phosphorylating multiple substrates mediating macrophage activation T lymphocyte specification, thus participating development Moreover, inhibition demonstrated to ameliorate certain disorders. Based on these studies, we suggest potential therapeutic target diseases valid candidate future research. Herein, first time, provide detailed review focuses roles pathogenesis

Language: Английский

A novel glycolysis-related gene signature for predicting prognosis and immunotherapy efficacy in breast cancer DOI Creative Commons

Rui Huang,

Liang Li, Kuei-Huei Lin

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 19, 2025

Previous studies have shown that glycolysis-related genes (GRGs) are associated with the development of breast cancer (BC), and prognostic significance GRGs in BC has been reported. Considering heterogeneity patients, which makes prognosis difficult to predict, fact glycolysis is regulated by multiple genes, it important establish evaluate new prediction models BC. In total, 170 were selected from GeneCards database. We analyzed data Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) database as a training set Gene Expression Omnibus (GEO) validation cohort. Based on overall survival expression levels GRGs, Cox regression analyses applied develop gene (GRPGs)-based model. Kaplan (KM) ROC performed assess performance this Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) used identify potential biological functions GRPGs. cBioPortal was explore tumor mutation burden (TMB). The immune dysfunction exclusion indicator (TIDE) estimate patient response checkpoint blockade (ICB). tumor-infiltrating cells (TICs) stromal quantitatively based profiles. constructed model 10 GRPGs (ADPGK, HNRNPA1, PGAM1, PIM2, YWHAZ, PTK2, VDAC1, CS, PGK1, GAPDHS) predict outcomes patients Patients divided into low- high-risk groups signature. AUC values curves 0.700 (1-year OS), 0.714 (3-year 0.681 (5-year OS). TMB TIDE showed group might respond better ICB. Additionally, combining signature clinical characteristics novel nomogram constructed. for combined 0.827 0.792 0.783 indicating an outstanding predictive performance. A built OS immunotherapeutic

Language: Английский

Citations

0
Trajectories of microbiome-derived bile acids in early life - Insights into the progression to islet autoimmunity DOI Creative Commons
Santosh Lamichhane, Alex M. Dickens, Tanja Buchacher

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

Recent studies reveal that gut microbes produce diverse bile acid conjugates, termed microbially conjugated acids (MCBAs). However, their regulation and health effects remain unclear. Here, we analyzed early-life MCBA patterns link to islet autoimmunity. We quantified 110 MCBAs in 303 stool samples collected longitudinally (3- 36 months) from children who developed one or more autoantibodies controls remained autoantibody-negative. Stool showed distinct age-dependent trajectories correlated with microbiome composition. Altered levels of ursodeoxycholic deoxycholic conjugates were linked autoimmunity as well modulated monocyte activation response immunostimulatory lipopolysaccharide Th17/Treg cell balance. These findings suggest influence immune development type 1 diabetes risk.

Language: Английский

Citations

0
Gaining new insights into the etiology of ulcerative colitis through a cross-tissue transcriptome-wide association study DOI Creative Commons
Shijie Ren,

Chaodi Sun,

Wen-Jing Zhai

et al.

Frontiers in Genetics, Journal Year: 2024, Volume and Issue: 15

Published: July 18, 2024

Background Genome-wide association studies (GWASs) have identified 38 loci associated with ulcerative colitis (UC) susceptibility, but the risk genes and their biological mechanisms remained to be comprehensively elucidated. Methods Multi-marker analysis of genomic annotation (MAGMA) software was used annotate on GWAS summary statistics UC from FinnGen database. Genetic performed identify genes. Cross-tissue transcriptome-wide study (TWAS) using unified test for molecular signatures (UTMOST) compare gene expression matrix (from Genotype-Tissue Expression Project) data integration. Subsequently, we FUSION select key individual tissues. Additionally, conditional joint conducted improve our understanding UC. Fine-mapping causal sets (FOCUS) employed accurately locate The results four genetic analyses (MAGMA, UTMOST, FOCUS) were combined obtain a set Finally, Mendelian randomization (MR) Bayesian colocalization determine relationship between To robustness findings, same approaches taken verify IEU. Results Multiple correction tests screened PIM3 as showed that posterior probability hypothesis 4 0.997 0.954 in validation dataset. MR inverse variance weighting method two single nucleotide polymorphisms (SNPs, rs28645887 rs62231924) included ( p < 0.001, 95%CI: 1.45-1.89). In dataset, result 1.19-1.72, indicating clear Conclusion Our validated its level may related UC, providing novel reference further improving current structure

Language: Английский

Citations

3
KLHL25-ACLY module functions as a switch in the fate determination of the differentiation of iTreg/Th17 DOI Creative Commons
Miaomiao Tian, Fengqi Hao, Xin Jin

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 21, 2025

The differentiation of Th17 and iTreg is tightly associated with fatty acid metabolism. TGFβ1-induced from Th0 relies on oxidation (FAO), whereas IL-6 TGFβ1 shifts metabolism to Th17-preferred synthesis (FAS). However, how reprograms remains unclear. Here, we unveiled that TGFβ1-activated JNK recruited the Klhl25 promoter by NF-YA. then phosphorylates histone H3 at Ser10 activate transcription, leading ubiquitination-dependent degradation ATP-citrate lyase (ACLY) switch FAS FAO, which supports generation. Whereas, upon signaling, NF-YA phosphorylated ERK, losing its DNA binding ability, shuts off TGFβ1-JNK-mediated transcription ACLY ubiquitination, thereby increasing supporting differentiation. This study demonstrated KLHL25-ACLY module functions as a in response signals, playing decisive role fate determination iTreg/Th17 responds signals regulate controlling ubiquitination transition acids metabolism, constitutes determinant for decision

Language: Английский

Citations

0
PIM kinase control of CD8 T cell protein synthesis and cell trafficking DOI Open Access
Julia M. Marchingo, Laura Spinelli, Shalini Pathak

et al.

Published: April 17, 2025

Integration of a large network kinase signalling pathways co-ordinates changes in the transcription, translation and metabolic events required for T cell activation differentiation. The present study explores role Serine/Threonine kinases PIM1 PIM2 controlling murine CD8 lymphocyte antigen receptor-mediated differentiation response to cytokines Interleukin 2 (IL-2) or IL-15. We show that PIM are dispensable programs controlled by antigen-receptor There is however selective context IL-2 regulation fate. One key insight was migratory capabilities effector cells, with Pim1 / Pim2 -deficient cells unable fully switch off naïve chemokine adhesion receptor program during were also needed sustain high expression glucose transporters SLC2A1 SLC2A3 maintain activity nutrient sensing mTORc1. Strikingly, did not have dominant impact on IL-2-driven transcriptional but rather selectively modulated protein synthesis shape cytotoxic proteomes. This reveals control highlights how regulated can phenotypes.

Language: Английский

Citations

0
Theoretical Studies of DNA Microarray Present Potential Molecular and Cellular Interconnectivity of Signaling Pathways in Immune System Dysregulation DOI Open Access
Jon Patrick T. Garcia, Lemmuel L. Tayo

Genes, Journal Year: 2024, Volume and Issue: 15(4), P. 393 - 393

Published: March 22, 2024

Autoimmunity is defined as the inability to regulate immunological activities in body, especially response external triggers, leading attack of tissues and organs host. Outcomes include onset autoimmune diseases whose effects are primarily due dysregulated immune responses. In past years, there have been cases that show an increased susceptibility other disorders patients who already experiencing same type disease. Research this field has started analyzing potential molecular cellular causes interconnectedness, bearing mind possibility advancing drugs therapies for treatment autoimmunity. With that, study aimed determine correlation four diseases, which 1 diabetes (T1D), psoriasis (PSR), systemic sclerosis (SSc), lupus erythematosus (SLE), by identifying highly preserved co-expressed genes among datasets using WGCNA. Functional annotation was then employed characterize these sets based on their relationship a whole elucidate biological processes, components, functions pathways they involved in. Lastly, drug repurposing analysis performed screen candidate repositioning could abnormal expression diseases. A total thirteen modules were obtained from analysis, majority associated with transcriptional, post-transcriptional, post-translational modification processes. Also, evaluation KEGG suggested possible role TH17 differentiation simultaneous Furthermore, clomiphene top regulating overexpressed hub genes; meanwhile, prilocaine under-expressed genes. This geared towards utilizing transcriptomics approaches assessment microarray data, different use traditional genomic analyses. Such research design investigating correlations may be first its kind.

Language: Английский

Citations

2
PIM Kinases as Potential Biomarkers and Therapeutic Targets in Inflammatory Arthritides DOI Open Access
Elisa Assirelli, Jacopo Ciaffi,

Valentina Scorcu

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3123 - 3123

Published: March 8, 2024

The Proviral Integration site for the Moloney murine leukemia virus (PIM)-1 kinase and its family members (PIM-2 PIM-3) regulate several cellular functions including survival, proliferation, apoptosis. Recent studies showed their involvement in pathogenesis of rheumatoid arthritis RA, while no are available on psoriatic (PsA) axial spondyloarthritis (axSpA). main objective this study is to assess expression PIM kinases inflammatory arthritides, correlation with proinflammatory cytokines, variation after treatment biologic disease-modifying anti-rheumatic drugs or JAK inhibitors. We evaluated PIM-1, -2, -3 at gene protein level, respectively, peripheral blood mononuclear cells serum patients PsA, axSpA, healthy individuals (CTR). All samples both level. PIM-1 was most expressed protein, PIM-3 least. levels differed between controls disease groups, reduced increased all compared controls. No difference found these molecules three different pathologies. were not modified 6 months therapy. In conclusion, our preliminary data suggest a deregulation pathway arthritides. In-depth role field warranted.

Language: Английский

Citations

1
PIM kinase control of CD8 T cell protein synthesis and cell trafficking DOI Creative Commons
Julia M. Marchingo, Laura Spinelli, Shalini Pathak

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 28, 2024

Abstract Integration of a large network kinase signalling pathways co-ordinates changes in the transcription, translation and metabolic events required for T cell activation differentiation. The present study explores role Serine/Threonine kinases PIM1 PIM2 controlling murine CD8 lymphocyte antigen receptor-mediated differentiation response to cytokines Interleukin 2 (IL-2) or IL-15. We show that PIM are dispensable programs controlled by antigen-receptor There is however selective context IL-2 regulation fate. One key insight was migratory capabilities effector cells, with Pim1 / Pim2 -deficient cells unable fully switch off naïve chemokine adhesion receptor program during were also needed sustain high expression glucose transporters SLC2A1 SLC2A3 maintain activity nutrient sensing mTORc1. Strikingly, did not have dominant impact on IL-2-driven transcriptional but rather selectively modulated protein synthesis shape cytotoxic proteomes. This reveals control highlights how regulated can phenotypes.

Language: Английский

Citations

1
PIM kinase control of CD8 T cell protein synthesis and cell trafficking DOI Open Access
Julia M. Marchingo, Laura Spinelli, Shalini Pathak

et al.

Published: July 24, 2024

Integration of a large network kinase signalling pathways co-ordinates changes in the transcription, translation and metabolic events required for T cell activation differentiation. The present study explores role Serine/Threonine kinases PIM1 PIM2 controlling murine CD8 lymphocyte antigen receptor-mediated differentiation response to cytokines Interleukin 2 (IL-2) or IL-15. We show that PIM are dispensable programs controlled by antigen-receptor There is however selective context IL-2 regulation fate. One key insight was migratory capabilities effector cells, with Pim1 / Pim2 -deficient cells unable fully switch off naïve chemokine adhesion receptor program during were also needed sustain high expression glucose transporters SLC2A1 SLC2A3 maintain activity nutrient sensing mTORc1. Strikingly, did not have dominant impact on IL-2-driven transcriptional but rather selectively modulated protein synthesis shape cytotoxic proteomes. This reveals control highlights how regulated can phenotypes.

Language: Английский

Citations

0
PIM kinase control of CD8 T cell protein synthesis and cell trafficking DOI Open Access
Julia M. Marchingo, Laura Spinelli, Shalini Pathak

et al.

Published: July 24, 2024

Integration of a large network kinase signalling pathways co-ordinates changes in the transcription, translation and metabolic events required for T cell activation differentiation. The present study explores role Serine/Threonine kinases PIM1 PIM2 controlling murine CD8 lymphocyte antigen receptor-mediated differentiation response to cytokines Interleukin 2 (IL-2) or IL-15. We show that PIM are dispensable programs controlled by antigen-receptor There is however selective context IL-2 regulation fate. One key insight was migratory capabilities effector cells, with Pim1 / Pim2 -deficient cells unable fully switch off naïve chemokine adhesion receptor program during were also needed sustain high expression glucose transporters SLC2A1 SLC2A3 maintain activity nutrient sensing mTORc1. Strikingly, did not have dominant impact on IL-2-driven transcriptional but rather selectively modulated protein synthesis shape cytotoxic proteomes. This reveals control highlights how regulated can phenotypes.

Language: Английский

Citations

0