Nature Genetics - High-resolution mapping of promoter-anchored chromosomal contacts in type 3 innate lymphoid cells (ILC3s), coupled with GWAS effector gene prioritization and functional studies,...

To profile promoter-anchored chromosomal contacts in ILC3s, we used our low-input DpnII-based PCHi-C protocol12,13 in ILC3s isolated from human tonsils (Fig. 1a). Significant promoter contacts were detected with CHiCAGO14 at single-fragment resolution, as well as after pooling ‘other end’ fragments into ~5-kb bins, while leaving the baited promoter-containing DpnII fragment unbinned. Using this approach, we detected 31,003 contacts between promoters and promoter-interacting regions (PIRs) at single-fragment resolution and 58,632 contacts in 5-kb bins (Fig. 1b and Supplementary Table 1; Data S1 and S2 at OSF15). Binning resulted in detection of longer-range contacts, as we reported previously in other cell types16 (Fig. 1c,d). For further analyses, we merged PIR sets detected at both resolutions (Methods). A joint UMAP embedding of ILC3 promoter interaction profiles with those detected in 17 abundant blood cell types using HindIII-based PCHi-C17 segregated ILC3s with other lymphoid cell types, consistent with patterns of promoter interactions reflecting lineage history (Extended Data Fig. 1a; Data S3 at OSF15; Methods). In total, more than half of PIRs (52.2%, 16,087 of 30,830) contacted at least one promoter in both ILC3s and another blood cell type (Data S3 at OSF15). Notably, the increased resolution afforded by using four-base cutter DpnII rather than...

Nature Genetics - High-resolution mapping of promoter-anchored chromosomal contacts in type 3 innate lymphoid cells (ILC3s), coupled with GWAS effector gene prioritization and functional studies,...

High-resolution mapping of promoter-anchored chromosomal contacts in type 3 innate lymphoid cells (ILC3s), coupled with GWAS effector gene prioritization and functional studies, identifies ILC3-linked...

High-resolution mapping of promoter-anchored chromosomal contacts in type 3 innate lymphoid cells (ILC3s), coupled with GWAS effector gene prioritization and functional studies, identifies ILC3-linked...

Vitamin D deficiency is associated with dysregulated alloimmune responses, but the mechanisms by which its active metabolite calcitriol shapes inna...

Innate lymphoid cells (ILCs) are emerging as critical modulators of inflammation in rheumatoid arthritis, contributing to both disease pathology and resolution. Group 3 ILCs (ILC3s) mirror TH17 cells in their production of IL-17A and IL-22, promoting fibroblast activation, neutrophil recruitment and synovial inflammatory cascades. By contrast, group 2 ILCs (ILC2s) engage reparative and immunoregulatory pathways via secretion of IL-9, IL-13 and IL-10. Lymphoid tissue inducer (LTi) ILCs contribute to ectopic lymphoid tissue neogenesis and stromal remodelling in early disease. Clinically, alterations in ILC subset composition correlate with disease activity, therapeutic responsiveness and inflammatory burden. Advances in high-dimensional immunophenotyping, spatial transcriptomics and single-cell multi-omics now enable precise mapping of ILC subsets and their effector programmes across peripheral blood and synovial tissue, supporting their use in biomarker discovery and treatment pipelines

ILC3s are innate immune cells that guard mucosal barriers by rapidly producing IL-22, IL-17, and GM-CSF. They reinforce epithelial integrity, orchestrate adaptive immunity, and promote tolerance. Xie et al. review their context-dependent functions encompassing both host protection and immunopathology, highlighting their therapeutic potential in mucosal diseases.