RORγt dendritic cells are a distinct lymphoid-derived lineage.
| Authors | |
| Abstract | How tolerogenic dendritic cell (DC) lineages are established to prevent inappropriate immune responses to commensals and food antigens remains unclear. We identify RORγt DCs in mice as a distinct lymphoid-derived lineage to safeguard intestinal tolerance. Using lineage tracing and single-cell transcriptomics, we unveiled bone marrow-resident progenitors, which include a RORγt innate lymphoid progenitor (RILP) that generates both ILC3s and RORγt DCs, and a pre-RORγt DC precursor committed exclusively to the RORγt DC lineage. RORγt DC development required the +7 kb enhancer, whose accessibility was ensured by the repressors REV-ERBα and REV-ERBβ, and depended on the transcription factors PRDM16 and PU.1 for lineage commitment. Loss of any of these regulators abrogated RORγt DC differentiation, reduced peripheral regulatory T (T) cell induction, and skewed toward T helper 2 responses. Together, these findings define murine RORγt DCs as a lymphoid-derived lineage whose enhancer- and transcription factor-driven development is essential for peripheral T cell-mediated immune homeostasis. |
| Year of Publication | 2026
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| Journal | Science immunology
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| Pages | eaed7439
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| Date Published | 01/2026
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| ISSN | 2470-9468
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| DOI | 10.1126/sciimmunol.aed7439
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| PubMed ID | 41591258
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