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A cis-element at the Rorc locus regulates the development of type 3 innate lymphoid cells
- Source :
- Frontiers in Immunology, Vol 14 (2023)
- Publication Year :
- 2023
- Publisher :
- Frontiers Media S.A., 2023.
-
Abstract
- BackgroundAs an important early source of IL-17A and IL-22 in immune responses, type 3 innate lymphoid cells (ILC3s) are critically regulated by the transcription factor retinoic-acid-receptor-related orphan receptor gamma t (RORγt). Previously, we have identified a crucial role of the conserved non-coding sequence 9 (CNS9), located at +5,802 to +7,963 bp of the Rorc gene, in directing T helper 17 differentiation and related autoimmune disease. However, whether cis-acting elements regulate RORγt expression in ILC3s is unknown.ResultsHere we show that CNS9 deficiency in mice not only decreases ILC3 signature gene expression and increases ILC1-gene expression features in total ILC3s, but also leads to generation of a distinct CD4+NKp46+ ILC3 population, though the overall numbers and frequencies of RORγt+ ILC3s are not affected. Mechanistically, CNS9 deficiency selectively decreases RORγt expression in ILC3s, which thus alters ILC3 gene expression features and promotes cell-intrinsic generation of CD4+NKp46+ ILC3 subset.ConclusionOur study thus identifies CNS9 as an essential cis-regulatory element controlling the lineage stability and plasticity of ILC3s through modulating expression levels of RORγt protein.
- Subjects :
- ILC3s
RORγt
CNS9
cis-element
plasticity
Immunologic diseases. Allergy
RC581-607
Subjects
Details
- Language :
- English
- ISSN :
- 16643224
- Volume :
- 14
- Database :
- Directory of Open Access Journals
- Journal :
- Frontiers in Immunology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.bf51c132db0b4eb3a1d6cc5a6158adfd
- Document Type :
- article
- Full Text :
- https://doi.org/10.3389/fimmu.2023.1105145