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The transcription factor NR4A3 (also known as NOR-1) is a member of the Nr4a family of nuclear receptors and is expressed in myeloid and lymphoid cells. Here, we have shown that Nr4a3 is essential for the migration of [CD103.sup.+] dendritic cells (DCs) to lymph nodes (LNs). Nr4a3-deficient mice had very few [CD103.sup.+] migratory DCs (mDCs) present in LNs, and mixed- chimera studies revealed that this migratory defect was cell intrinsic. We further found that [CD103.sup.+] DCs from Nr4a3- deficient mice displayed a marked loss of surface expression of the chemokine CCR7. This defect in CCR7 expression was confined to [CD103.sup.+] DCs, as CCR7 expression on T lymphocytes was unaffected. Moreover, CCR7 was not induced on [CD103.sup.+] DCs from Nr4a3-deficient mice in response to either administration of the TLR7 agonist R848 or infection with Citrobacter rodentium in vivo. The transcription factor FOXO1 has been shown to regulate CCR7 expression. We found that FOXO1 protein was reduced in Nr4a3-deficient DCs through an AKT-dependent mechanism. Further, we found a requirement for NR4A3 in the maintenance of homeostatic mitochondrial function in [CD103.sup.+] DCs, although this is likely independent of the NR4A3/FOXO1/CCR7 axis in the regulation of DC migration. Thus, NR4A3 plays an important role in the regulation of [CD103.sup.+] mDCs by regulating CCR7-dependent cell migration., Introduction The intestine has a mucosal surface that directly interacts with large quantities of food antigens and microorganisms daily. As a consequence, the gut is the accessible entry site for [...]