Unveiling metabolite and sensory receptor pathways to modulate autoimmune inflammation

Autoimmune and autoinflammatory diseases arise from complex interactions between host genetic susceptibility and environmental factors, particularly the gut microbiota and its metabolites. Genome-wide association studies (GWAS) have identified numerous disease-associated genetic variants and single nucleotide polymorphisms affecting immune regulation, epithelial barrier function, and inflammatory signaling. However, genetic risk alone is insufficient to explain disease onset, heterogeneity, and progression, underscoring the importance of downstream sensing mechanisms that translate environmental and metabolic cues into immune responses.Recent advances highlight the pivotal role of microbiota-derived metabolites, including short-chain fatty acids, bile acids, tryptophan metabolites, and other microbial products, in shaping innate and adaptive immunity. These signals are detected by a diverse array of receptors, such as pattern recognition receptors (TLRs and NOD-like receptors), G protein-coupled receptors (e.g., GPR43, GPR109A, SUCNR1), and nuclear receptors (e.g., FXR, TGR5, AHR, PXR, and VDR). Dysregulation of these pathways contributes to chronic inflammation, altered Treg/Th17 balance, inflammasome activation, and tissue damage.In addition to classical immune and metabolic receptors, emerging evidence identifies transient receptor potential (TRP) channels as critical sensory receptors linking microbial metabolites, inflammatory mediators, and tissue stress to immune and neuroimmune responses. TRP channels expressed in epithelial cells, immune cells, and sensory neurons can rapidly translate chemical, metabolic, and physical stimuli into calcium signaling, thereby modulating cytokine production, barrier integrity, pain, and inflammation. Genetic variants and disease-associated polymorphisms may further influence TRP channel expression and function, adding another layer of complexity to immune dysregulation.Original articles and reviews submitted to this Research Topic are expected to:- Provide an integrated platform for original research and reviews on how genetic variants, microbiota-derived metabolites, and immune and sensory receptors (including TRP channels) interact to drive autoimmune and autoinflammatory diseases.- Welcome mechanistic studies that clarify receptor-mediated pathways linking microbiota signals, sensory-immune communication, and immune dysregulation.- Encourage multi-omics approaches (e.g., genomics, metagenomics, metabolomics, transcriptomics, proteomics) to map host–microbiota–receptor interactions and disease signatures.- Invite translational research connecting experimental findings with patient cohorts, clinical phenotypes, and disease stratification.- Include therapeutic perspectives and intervention studies targeting immune/sensory receptor signaling (including TRP channels) to modulate inflammation.- Identify novel mechanisms, biomarkers, and therapeutic targets for immune-mediated inflammatory diseases by bridging genetics, microbiota research, and sensory–immune signaling.Please note that articles solely focused on bioinformatics, without experimental validation or an immunological focus, are out of scope for this journal. Topic editors: Hiroshi Mihara, Ammar Boudaka, Mizuho A Kido, Kunitoshi Uchida, Makiko Kashio, Reona Aijima Source: https://www.frontiersin.org/research-topics/78638/unveiling-metabolite-and-sensory-receptor-pathways-to-modulate-autoimmune-inflammation