Personalized Gut-Liver Microphysiological System Maps Donor-Specific Tissue Resident Immunity and Reveals a Conserved Metabolic Crosstalk
Uslu, M.; Ran, R.; Siddiqui, M. F.; Liang, J.; Raechal, L.; Dogsa, M.; Perrot, C.; Lieberman, L. A.; Brubaker, D. K.; Trapecar, M.
Show abstract
Tissue-resident immune (TRI) niches are unique to tissues and greatly vary between individuals. We built a personalized gut-liver microphysiological system (MPS) to recapitulate these profiles, combining primary colon epithelium, hepatocytes, and autologous CD45 TRI cells of two donors. Single-cell RNA-seq of colon and liver revealed distinct TRI profiles and predicted responses distinct between donors. Co-culture established organ and donor-specific immune programs: colonic epithelium induced Th1/Th17 polarization in Donor 1 but B cell differentiation in Donor 2. Gut-liver crosstalk in all donors converged on a retinoid-bile acid metabolic axis with a muted inflammatory set-point, indicating that circulating metabolites can override baseline immune differences. Microbial agonist challenges of gut compartments revealed distinct liver responses: Poly(I:C) induced a uniform type-I/III interferon burst, LPS triggered a stronger response in Donor 1, and 5-OP-RU selectively activated Donor 2. Our personalized, immune-competent gut-liver MPS demonstrates that a conserved metabolic dialogue coexists with and is modulated by TRI profiles. This work provides a blueprint for exploring immunometabolic diseases and precision therapeutics in multi-organ models reflecting human immune diversity.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Multiomic analysis reveals cellular and epigenetic plasticity in intestinal pouches of ulcerative colitis patients 95%
- Generation of functional ciliates cholangiocytes from human pluripotent stem cells 95%
- The immune profile of circulating autoreactive CD4 T cells is imprinted through tissue activation during autoimmune liver diseases 95%
Similar papers in this journal
- Human macrophage polarization determines bacterial persistence of Staphylococcus aureus in a liver-on-chip-based infection model 95%
- Single-Cell Epitope-Transcriptomics Reveal Lung Stromaland Immune Cell Response Kinetics to Nanoparticle delivered RIG-I and TLR4 Agonists 94%
- Soluble ECM promotes organotypic formation in lung alveolar model 94%
Similar papers in this journal
- A 3D in vitro model of the human hepatobiliary junction 94%
- A subset of pro-inflammatory CXCL10+ LILRB2+ macrophages derives from recipient monocytes and drives renal allograft rejection 94%
- Genetically-programmed Hypervesiculation of Lactiplantibacillus plantarum Increases Production of Bacterial Extracellular Vesicles with Therapeutic Efficacy in a Preclinical Inflammatory Bowel Disease Model 94%
Similar papers in this journal
- Nutritional deficiency recapitulates intestinal injury associated with environmental enteric dysfunction in patient-derived Organ Chips 95%
- Immunometabolic cues recompose and reprogram the microenvironment around biomaterials 94%
- Human spinal cord organoids exhibiting neural tube morphogenesis for a quantifiable drug screening system of neural tube defects 93%
Similar papers in this journal
- Macrophage Immune-Competent Colon Assembloids for Functional Interrogation of Neuroinflammation-Induced Colonic Dysmotility 96%
- Single-cell lineage trajectory defines CDK inhibitor-sensitive cells-of-origin in esophageal squamous cell cancer 92%
- Eicosanoids in the pancreatic tumor microenvironment: a multicellular, multifaceted progression 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.