Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1310509 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:While intestinal stem cells (ISCs) are essential for epithelial homeostasis, their dynamic regulation during immune-mediated injury remains undefined. Jejunal intestinal stem cell (ISC) proliferative suppression emerges as a pathological hallmark of oral EGFR tyrosine kinase inhibitors (TKIs), propelling chemokine-directed migration of T/B lymphocytes from Peyer's patches. Genetic ablation of adaptive immunity reversed ISC suppression and accelerated mucosal repair. Spatial transcriptomics revealed enhanced ISC-adaptive immune cell crosstalk in the jejunum. Ex vivo modeling demonstrated activated T cells directly impair ISC survival through IFN-γ and TNF-α, with JAK/STAT signaling constituting the critical downstream effector. Targeted JAK inhibition prevented T/B cell-mediated pathology while exhibiting dual efficacy: mitigating EGFRi–induced diarrhea without substantially compromising antitumor efficacy. This work redefines TKI-induced enteropathy as an immune-driven pathology and identifies JAK inhibition as the first mechanism-based supportive therapy, establishing a paradigm for precision management of targeted therapy toxicities.
2025-08-06 | PXD066986 |
Project description:Infectious enteritis is often accompanied with immuno-disorder of intestinal immune cells caused by microbials infection. Trained immunity is classically characterized by long-term functional reprogramming of innate immune cells to combat infectious diseases. However, whether the induction of trained immunity plays a role in protecting infectious enteritis remains largely unknown. Here, through establishing an in vivo β-glucan training and E. piscicida infection model in zebrafish, we observe that induction of trained immunity could alleviate bacterial infection-caused enteritis. Moreover, we identify intestinal complement C3 as a crucial target of trained immunity and could be amplified in response to bacterial infection. Furthermore, we reveal that trained immunity could reverse the reduction of intestinal Th17 cells in C3-dependent manner to alleviate infectious enteritis. Taken together, our results uncover the role of complement C3-mediated trained immunity in maintaining Th17 cells and intestine homeostasis, and provide a theoretical strategy for immunotherapies of infectious enteritis.
2025-05-01 | GSE285528 | GEO
Project description:In rheumatoid arthritis (RA), inflammation and joint destruction are exacerbated by a complicated interaction among immune cells, synovial fibroblasts and bone cells. It remains to be elucidated which cell-cell interaction critically drives the pathogenesis of RA and serves as a therapeutic target for synthetic disease modifying antirheumatic drugs (DMARDs) such as janus kinase (JAK) inhibitors. we performed a scRNA-seq analysis of the synovium of collagen-induced arthritis (CIA) mice treated with JAK inhibitor, followed by a computational analysis to identify the drug target cells and signaling pathways in vivo
2024-08-23 | GSE224221 | GEO
Project description:Early-life antibiotic exposure perturbs the intestinal microbiota, alters innate intestinal immunity, and accelerates type 1 diabetes development in the NOD mouse model. Here we found that maternal cecal microbiota transfer (CMT) to NOD mice with early-life antibiotic perturbation partially rescued the induced T1D acceleration. The restoration effects on the intestinal microbiome were substantial and persistent, remediating the antibiotic-depleted diversity, relative abundance of particular taxa, and metabolic pathways. CMT also protected against perturbed cecal and serum metabolites and normalized innate and adaptive immune effectors. CMT restored patterns of ileal microRNA and histone regulation of gene expression and exon-splicing. Based on the analyses of experimental data, we propose an innate intestinal immune network involving CD44, TLR2, and Reg3g, as well as their multiple microRNA and epigenetic regulators that sense intestinal signaling by the gut microbiota. This regulation affects downstream immunological tone, leading to protection against the tissue-specific T1D injury.
2021-09-02 | E-MTAB-9982 | biostudies-arrayexpress
Project description:Mycophenolate mofetil (MMF) has been widely prescribed for neuromyelitis optica spectrum disorders (NMOSD) although some patients experience severe gastrointestinal (GI) side effects following MMF administration. Our study investigated the potential mechanisms of this toxicity in NMOSD patients. We constructed MMF-induced colitis mouse model and produced a multi-omic dataset in which microbiome and metabolome analysis from the mouse GI tract to decipher the mechanisms of MMF GI toxicity. Further, 17 female NMOSD patients treated with MMF were prospectively enrolled and grouped according to the diarrhea symptom as non-diarrhea NMOSD group (NM) and diarrhea NMOSD group (DNM) as well as healthy controls (HC, 12 female). The gut microbiota was analyzed using 16S rRNA sequencing of stool samples. In the mouse model, we found that vancomycin administration drastically altered the colon content metabolomes and microbiomes and prevented MMF-induced body weight loss, cecal and colon tissue injury. Bacteroidetes and Firmicutes converted phenyl-beta-D-glucuronide (MPAG) to mycophenolic acid (MPA) that could result in damaged intestinal tissue. We also demonstrated that the alpha diversity in the DNM group was increased and this was accompanied by increased Firmicutes and Proteobacteria abundance. Collectively, these results reveal that alterations of the gut microbiome and metabolome contribute to MMF-induced colitis. Modifying of the gut microbiome and metabolome may alleviate MMF-induced GI toxicity in NMOSD patients.
2024-06-18 | MTBLS4392 | MetaboLights
Project description:Bacterial flagellin is a dominant innate immune activator of the intestine. Therefore, we examined the role of the intracellular flagellin receptor, NLRC4, in protecting the gut and/or driving inflammation. In accord with NLRC4 acting via transcription-independent pathways, loss of NLRC4 did not reduce the rapid robust changes in intestinal gene expression induced by flagellin administration. Loss of NLRC4 did not alter basal intestinal homeostasis nor predispose mice to development of colitis upon administration of an anti-IL-10R monoclonal antibody. However, in response to epithelial injury induced by dextran sulfate sodium (DSS), loss of NLRC4 resulted in more severe disease indicating a role for NLRC4 in protecting the gut. Moreover, loss of NLRC4 resulted in increased mortality in response to flagellate, but not aflagellate Salmonella infection. Thus, despite not being involved in rapid intestinal gene remodeling upon detection of flagellin, NLRC4-mediated inflammasome activation protects mice from mucosal and systemic challenges Flagellin (FliC) from WT Salmonella enterica serovar Typhimurium (SL3201, fljB–) was purified through sequential cation and anion-exchange chromatography and purity was verified as previously described 4. WT, T5KO, N4KO and T5/N4-DKO mice (n=6) were given either 0.2 mL PBS or flagellin (10μg/mouse in 0.2 mL PBS) intraperitoneally. After 1h, mice were euthanized and colon was taken and stored in RNAlater (Invitrogen) for 1 day. Total mRNA was isolated from colonic tissues using TRIzol (Invitrogen) and purified using the RNeasy® Plus Mini kit (Qiagen) according to the manufacturer’s instructions
2012-01-01 | E-GEOD-34492 | biostudies-arrayexpress
Project description:Dampness heat diarrhea (DHD) is the leading cause in calves with diarrhea in traditional Chinese medicine (TCM). However, the methods for detecting DHD diarrhea remain subjective or infective. To address this issue, the calves with dampness heat diarrhea were collected and the plasma proteomic was analyzed using data-independent acquisition (DIA)-mass spectrometry- based proteomics. The analysis revealed a total of 52 differentially expressed proteins that were uniquely altered in the DHD calves’ plasma, compared to the control. Bioinformatics analysis showed that these altered proteins were involved in a wide range of biological processes, such as intestinal immune network for IgA production, purine metabolism and PI3K signaling pathway, which implying their potential roles in DHD.
2022-10-14 | PXD027099 | Pride
Project description:Bacterial flagellin is a dominant innate immune activator of the intestine. Therefore, we examined the role of the intracellular flagellin receptor, NLRC4, in protecting the gut and/or driving inflammation. In accord with NLRC4 acting via transcription-independent pathways, loss of NLRC4 did not reduce the rapid robust changes in intestinal gene expression induced by flagellin administration. Loss of NLRC4 did not alter basal intestinal homeostasis nor predispose mice to development of colitis upon administration of an anti-IL-10R monoclonal antibody. However, in response to epithelial injury induced by dextran sulfate sodium (DSS), loss of NLRC4 resulted in more severe disease indicating a role for NLRC4 in protecting the gut. Moreover, loss of NLRC4 resulted in increased mortality in response to flagellate, but not aflagellate Salmonella infection. Thus, despite not being involved in rapid intestinal gene remodeling upon detection of flagellin, NLRC4-mediated inflammasome activation protects mice from mucosal and systemic challenges
2012-01-01 | GSE34492 | GEO
Project description:Immune checkpoint inhibitors (CPIs) have revolutionised cancer treatment, with previously untreatable disease now amenable to potential cure. Combination regimens of anti-CTLA-4 and anti-PD-1 show enhanced efficacy but are prone to off-target immune-mediated tissue injury, particularly at the barrier surfaces. CPI-induced colitis is a common and serious complication. To probe the impact of immune checkpoints on intestinal homeostasis, mice were challenged with anti-CTLA-4 and anti-PD-1 immunotherapy and manipulation of the intestinal microbiota. Colonic immune responses were profiled using bulk RNA-sequencing.
2023-09-08 | GSE222843 | GEO