Malysheva, Valeriya, Ray-Jones, Helen, Lakes, Nora, Brown, Rachel A., Cazares, Tareian A., Clay, Owen, Ohayon, David E., Artemov, Pavel, Wayman, Joseph A., Yang, Zi F., and others. (2026) High-resolution promoter interaction analysis implicates genes involved in activation of type 3 innate lymphoid cells in immune disease risk. Nature Genetics, 58 . pp. 1953-1966. ISSN 1061-4036. E-ISSN 1546-1718. (doi:10.1038/s41588-026-02681-0) (KAR id:115987)
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| Official URL: https://doi.org/10.1038/s41588-026-02681-0 |
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Abstract
Innate lymphoid cells (ILCs) are rare tissue-resident lymphocytes that functionally mirror cells of CD4+ T helper lineage but lack antigen receptors.
Type 3 ILCs (ILC3s) are enriched at barrier sites, regulating inflammation and promoting tissue integrity. Here we profile the promoter-anchored
chromosomal contacts of primary human ILC3s using low-input, highresolution targeted chromosome conformation capture and compare them with those in CD4+ T cells. We use these data to link Crohn’s disease genome-wide association study variants with target genes, implicating both known and unanticipated candidates, including CLN3, a causal gene for Batten disease. We show that Cln3 overexpression in a mouse ILC3-like cell line alters stimulation-induced transcriptional programs and cytokine secretion. Extending our approach to five additional immune genome-wide association study traits reveals enrichment for regulators of ILC3 activation. Our work develops methods, maps long-range gene regulation in ILC3s, and prioritizes immune disease risk genes with roles in this clinically relevant immune cell type.
| Item Type: | Article |
|---|---|
| DOI/Identification number: | 10.1038/s41588-026-02681-0 |
| Subjects: | Q Science |
| Institutional Unit: | Schools > School of Natural Sciences > Biosciences |
| Former Institutional Unit: |
There are no former institutional units.
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| Funders: | University of Kent (https://ror.org/00xkeyj56) |
| Depositing User: | Frances Burden |
| Date Deposited: | 24 Aug 2026 15:23 UTC |
| Last Modified: | 28 Aug 2026 14:32 UTC |
| Resource URI: | https://kar.kent.ac.uk/id/eprint/115987 (The current URI for this page, for reference purposes) |
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