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Distinct Gene Regulatory Pathways for Human Innate versus Adaptive Lymphoid Cells
Olivia I Koues1, Patrick L Collins1, Marina Cella1
1Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Cell
|May 10, 2016
Summary
Human innate lymphoid cells (ILCs) are crucial sentinels. This study reveals their distinct lineages and shared functional circuits with T helper (Th) cells, uncovering new regulatory insights.
Area of Science:
- Immunology
- Cell Biology
- Genetics
Background:
- Innate lymphoid cells (ILCs) are vital mucosal sentinels, but their human lineage and functional relationships to T helper (Th) cells remain unclear.
- Understanding ILCs is crucial for comprehending tissue homeostasis and immune responses.
Purpose of the Study:
- To elucidate the gene regulatory circuitries of human ILC subsets.
- To compare the lineage and functional kinships of human ILCs with their T helper (Th) cell counterparts.
Main Methods:
- Analysis of gene regulatory circuitries in four human ILC-Th counterpart subsets from mucosal environments.
- Identification of super-enhancers and cell-identity genes.
Main Results:
- Each human ILC subset diverges as a distinct lineage from Th and natural killer cells.
- ILCs share functional polarization circuitry with their Th counterparts.
- Super-enhancers regulate signature cytokines and identify potential autoimmune disease SNP associations.
Conclusions:
- Human ILCs represent distinct lineages with shared functional programming with Th cells.
- Gene regulatory insights provide novel understanding of ILC function and potential links to autoimmune diseases.
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