{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE325nnn/GSE325926/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325926"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"LINGO4 coordinates intrinsic IL-22 production and microbiota-dependent ILC3 homeostasis to regulate intestinal immunity","description":"LINGO4 is a leucine-rich repeat and immunoglobulin-like domain-containing transmembrane protein encoded immediately adjacent to Rorc, the gene for RORγt, raising the possibility that it contributes to the biology of RORγt⁺ lymphocytes. However, its impact on these cells and resistance to enteric infections has remained unknown. Here, we identify LINGO4 as a critical regulator of group 3 innate lymphoid cells (ILC3s). Lingo4–/– ILC3s exhibit a profound, cell-intrinsic defect in IL-22 production linked to impaired STAT3 activation, mitochondrial dysfunction, elevated reactive oxygen species, and increased apoptosis. In vivo, Lingo4 deficiency also drives a dysbiotic gut microbiota, resulting in an additional, microbiota-dependent loss of ILC3s. These combined defects increase susceptibility to C. difficile and C. rodentium, while Lingo4–/– driven IL-22 reduction confers protection against S. Typhimurium. Immunoprecipitation of tagged LINGO4 reveals interaction networks enriched in mitochondrial pathways, providing mechanistic insight into its role in ILC3 metabolic fitness and intestinal immunity.","dates":{"publication":"2026/04/02"},"accession":"GSE325926","cross_references":{"GSM":["GSM9617320","GSM9617318","GSM9617319","GSM9617316","GSM9617317","GSM9617314","GSM9617315","GSM9617313"],"GPL":["24247"],"GSE":["325926"],"taxon":["Mus musculus"]}}