GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE326nnn/GSE326459/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE326459GEOGSEfalseSlc44a2 deficiency unveils an IFN-I–dependent feedback control of pDC egressPlasmacytoid 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.2026/07/15GSE326459GSM9632034GSM9632033GSM9632032GSM9632031GSM9632030GSM9632029GSM9632028GSM963202723479326459Mus musculus[42360155]