NF-κB Inflammatory Activation

Gene co-expression module in Pericytes

View this module in SCUBA

Why this annotation

IL32 is a pro-inflammatory cytokine strongly induced in IBD and known to activate NF-κB and MAPK pathways. CTSS (cathepsin S) is a lysosomal cysteine protease involved in antigen presentation and inflammatory tissue remodeling. HIF1A is the master hypoxia transcription factor, also activated by NF-κB during inflammation. TAPBP (tapasin) is an MHC class I antigen presentation component. OSMR (oncostatin M receptor) mediates OSM signaling, a key inflammatory cytokine in IBD that activates pericytes/stromal cells. EFHD2 (swiprosin-1) is involved in immune cell activation and cytoskeletal regulation. LAP3 (leucine aminopeptidase 3) is an interferon-stimulated gene. TMEM165 is a Golgi Ca2+/H+ antiporter involved in glycosylation. The module has the highest inflammation delta for CD (0.640) and strong UC signal, with clear reversal in remission. The combination of IL32, CTSS, HIF1A, TAPBP, OSMR, and LAP3 defines a cytokine/NF-κB/hypoxia inflammatory activation program in pericytes. This is distinct from the ER stress modules (M70, M68, M40) and the ECM remodeling module (M18), representing a more direct inflammatory signaling response. Concordant inflammatory genes: IL32, CTSS, HIF1A, TAPBP, OSMR, LAP3, EFHD2 (7/8).

Genes

CTSS, EFHD2, HIF1A, IL32, LAP3, OSMR, TAPBP, TMEM165

Most correlated modules

• ER Stress Response · correlation 0.93
• ER Protein Folding · correlation 0.87
• ER Chaperone UPR · correlation 0.86
• Inflammatory ECM Remodeling · correlation 0.84
• TGF-β Cytoskeletal Remodeling · correlation 0.79
• Basement Membrane Remodeling · correlation 0.75
• Inflammatory Pericyte Activation · correlation 0.75

Module annotations were drafted by a large language model from the module's genes, then reviewed and approved by a domain expert. See sources & licences.