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Developmental Acquisition of Regulomes Underlies Innate Lymphoid Cell Functionality.
Han-Yu Shih1, Giuseppe Sciumè1, Yohei Mikami1
1Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Cell
|May 10, 2016
Summary
Innate lymphoid cells (ILCs) and T helper (Th) cells share regulatory DNA elements. This study reveals extensive shared regulatory circuitry between these innate and adaptive immune cells, despite different developmental paths.
Area of Science:
- Immunology
- Molecular Biology
- Genomics
Background:
- Innate lymphoid cells (ILCs) are crucial for immune responses, mirroring functions of adaptive CD4(+) T helper (Th) cells.
- Understanding the relationship between ILC subsets and Th cells is vital for comprehending immune system regulation.
Purpose of the Study:
- To investigate the relationship between ILC subsets and Th cell counterparts by measuring genome-wide chromatin accessibility.
- To identify shared regulatory circuitry between innate and adaptive immune compartments.
Main Methods:
- Genome-wide chromatin accessibility profiling was performed on ILCs and CD4(+) T cells.
- Analysis focused on regulatory regions near effector genes.
- A type-2-infection model was used to study Th cell differentiation.
Main Results:
- Chromatin near effector genes is selectively accessible in ILCs before activation, acquired during development.
- In contrast, naive CD4(+) T cells undergo significant chromatin remodeling during Th cell differentiation.
- Th2 cells show substantial convergence towards ILC2 regulomes, indicating shared regulatory elements.
Conclusions:
- Extensive sharing of regulatory circuitry exists between innate (ILCs) and adaptive (Th cells) immune compartments.
- Chromatin accessibility patterns in ILCs are largely established during development and stable upon activation.
- Immune cell differentiation involves significant chromatin remodeling, leading to convergence in regulatory landscapes.
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