{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE326nnn/GSE326459/"]},"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=GSE326459"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Slc44a2 deficiency unveils an IFN-I–dependent feedback control of pDC egress","description":"Plasmacytoid dendritic cells (pDCs) are a specialized subset of innate immune cells capable of sensing viral nucleic acids and rapidly producing large amounts of type I interferons (IFN-I). However, excessive IFN-I production can cause various immunopathogenic conditions. The capacity for IFN-I production by pDCs is tightly regulated, yet the underlying mechanisms remain incompletely understood. Here, we describe two levels of negative regulatory mechanisms controlling IFN-I production by pDCs. First, we identified SLC44A2 as a negative regulator of IFN-I production. SLC44A2 was highly expressed in resting pDCs but significantly downregulated upon activation. Deficiency of SLC44A2 led to excessive IFN-I production. Mechanistically, SLC44A2 may restrict IFN-I production by exporting threonine, asparagine, and glutamine, amino acids that we found to be essential for IFN-I production in pDCs. Second, we uncovered an IFN-I-dependent negative feedback mechanism controlling pDC egress. Excessive IFN-I restrained pDC migration by downregulating CCR2 and CCR5. This feedback was generally observed during viral infections, autoimmune diseases, and in Slc44a2-deficient mice. Taken together, these two regulatory mechanisms are essential for maintaining pDC homeostasis and preventing systemic overactivation of IFN-I responses.","dates":{"publication":"2026/07/15"},"accession":"GSE326459","cross_references":{"GSM":["GSM9632034","GSM9632033","GSM9632032","GSM9632031","GSM9632030","GSM9632029","GSM9632028","GSM9632027"],"GPL":["23479"],"GSE":["326459"],"taxon":["Mus musculus"],"PMID":["[42360155]"]}}