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However, excessive IFN\u2010I production can cause various immunopathogenic conditions. The capacity for IFN\u2010I production by pDCs is tightly regulated, yet the underlying mechanisms remain incompletely understood. Here, we describe two levels of negative regulatory mechanisms controlling IFN\u2010I production by pDCs. First, we identified SLC44A2 as a negative regulator of IFN\u2010I production.\n                    <jats:italic>Slc44a2<\/jats:italic>\n                    was highly expressed in resting pDCs but significantly downregulated upon activation. Deficiency of\n                    <jats:italic>Slc44a2<\/jats:italic>\n                    led to excessive IFN\u2010I production. Mechanistically, SLC44A2 may restrict IFN\u2010I production by exporting threonine, asparagine, and glutamine, amino acids that we found to be essential for IFN\u2010I production in pDCs. Second, we uncovered an IFN\u2010I\u2010dependent negative feedback mechanism controlling pDC egress. Excessive IFN\u2010I restrained pDC migration by downregulating CCR2 and CCR5. This feedback was generally observed during viral infections, autoimmune diseases, and in\n                    <jats:italic>Slc44a2<\/jats:italic>\n                    \u2010deficient mice. Taken together, these two regulatory mechanisms are essential for maintaining pDC homeostasis and preventing systemic overactivation of IFN\u2010I responses.\n                  <\/jats:p>","DOI":"10.1002\/advs.76325","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T12:36:45Z","timestamp":1782477405000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Slc44a2<\/i>\n                    Deficiency Unveils an IFN\u2010I\u2013Dependent Feedback Control of pDC Egress"],"prefix":"10.1002","volume":"13","author":[{"given":"Ruiqun","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Membrane Biology School of Pharmaceutical Sciences Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education) Tsinghua Medicine Tsinghua University  Beijing China"},{"name":"Institute for Immunology School of Basic Medical Sciences Tsinghua 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