Peer-Reviewed Publication
Nat Genet2026August 4, 2026Journal Article
High-resolution promoter interaction analysis implicates genes involved in activation of type 3 innate lymphoid cells in immune disease risk.
Valeriya Malysheva1,2,3,4,5,6, Helen Ray-Jones7,8,9,10, Nora Lakes11,12,13, Rachel A Brown14,15, Tareian A Cazares11,16,17, Owen Clay13,18,19, David E Ohayon13, Pavel Artemov7,8,20, Joseph A Wayman16, Zi F Yang16, Monica Della Rosa7,8,21, Carmen Petitjean7,8,22,23, Clarissa Booth24, Joseph I J Ellaway7,8,25, Jenna R Barnes12,13, Andrew W Dangel14,15, Ankita Saini14,15, William R Orchard7,26,27, Xiaoting Chen13, Sreeja Parameswaran13, Frances Burden28,29,30, Mattia Frontini28,29,31, Takashi Nagano32,33,34, Peter Fraser32,35, Stefan Schoenfelder32, Matthew T Weirauch11,12,13,36,37,38,39, Leah C Kottyan11,12,13,36,39, David F Smith36,40,41, Nick Powell42, Jill M Weimer24, Eugene M Oltz14,15, Chris Wallace43,44, Emily R Miraldi11,12,16,36,38, Stephen N Waggoner45,46,47,48,49, Mikhail Spivakov50,51
1MRC Laboratory of Medical Sciences, London, UK. valeriya.malysheva@vib.be.
2Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK. valeriya.malysheva@vib.be.
3VIB, Center for Molecular Neurology, Antwerp, Belgium. valeriya.malysheva@vib.be.
4Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium. valeriya.malysheva@vib.be.
5VIB, Center for AI and Computational Biology, Leuven, Belgium. valeriya.malysheva@vib.be.
6Trinity Hall, University of Cambridge, Cambridge, UK. valeriya.malysheva@vib.be.
7MRC Laboratory of Medical Sciences, London, UK.
8Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK.
9VIB, Center for Molecular Neurology, Antwerp, Belgium.
10Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
11Immunology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
12Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
13Division of Human Genetics and Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
14Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA.
15Pelotonia Institute for Immuno-Oncology, The Ohio State University, Columbus, OH, USA.
16Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
17Eli Lilly and Company, Indianapolis, IN, USA.
18Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
19Section of Pediatric Rheumatology, Department of Pediatrics, Wake Forest School of Medicine, Winston-Salem, NC, USA.
20Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.
21NeoGenomics, Cambridge, UK.
22British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
23Heart and Lung Research Institute, University of Cambridge, Cambridge, UK.
24Center for Genetics and Rare Diseases, Sanford Research, Sioux Falls, SD, USA.
25European Bioinformatics Institute, Hinxton, UK.
26University of Cambridge, Cambridge, UK.
27Cancer Research UK Cambridge Research Institute, Cambridge, UK.
28Department of Haematology, University of Cambridge, Cambridge, UK.
29National Health Service (NHS) Blood and Transplant, Cambridge, UK.
30University of Kent, Canterbury, UK.
31Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter Medical School, Exeter, UK.
32The Babraham Institute, Cambridge, UK.
33Laboratory for Nuclear Dynamics, Institute for Protein Research, Osaka University, Osaka, Japan.
34Institute of Medical Science, University of Tokyo, Tokyo, Japan.
35Department of Biological Sciences, Florida State University, Tallahassee, FL, USA.
36Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
37Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
38Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
39Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
40Department of Otolaryngology, Head and Neck Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
41Divisions of Pediatric Otolaryngology and Pulmonary & Sleep Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
42Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
43MRC Biostatistics Unit, Cambridge Biomedical Campus, Cambridge Institute of Public Health, Cambridge, UK.
44Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK.
45Immunology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH, USA. stephen.waggoner@cchmc.org.
46Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH, USA. stephen.waggoner@cchmc.org.
47Division of Human Genetics and Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. stephen.waggoner@cchmc.org.
48Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. stephen.waggoner@cchmc.org.
49Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA. stephen.waggoner@cchmc.org.
50MRC Laboratory of Medical Sciences, London, UK. mikhail.spivakov@lms.mrc.ac.uk.
51Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK. mikhail.spivakov@lms.mrc.ac.uk.
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, high-resolution targeted chromosome conforma…
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