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Updated: Jun 19, 2026

Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation
Published on: June 27, 2017
Common γ-chain cytokines induce an epigenomically plastic precursor-like KIT+ ILC2 state linked to immune disease
Simone E M Olsthoorn1, Anne Onrust-Van Schoonhoven1, Marjolein J W de Bruijn1
1Department of Pulmonary Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Background:
Group 2 innate lymphoid cells (ILC2s) are key effector cells of type 2 immunity. A subset of ILC2s, which expresses KIT (CD117), display increased phenotypic plasticity and have previously been linked to severe asthma and psoriasis. However, the molecular mechanisms promoting a KIT+ ILC2 state remain poorly understood.
Objective:
We defined the molecular basis for the enhanced plasticity of KIT+ ILC2s and identified signals that induce this phenotype, including links with immune disease susceptibility.
Methods:
We combined bulk as well as single-cell transcriptome (RNA sequencing) and epigenome (assay for transposase-accessible chromatin using sequencing) analysis with in vitro culture assays using primary human KIT+ or KITneg ILC2s and multipotent ILC progenitors. Epigenomic data were integrated with genetic risk variants for major human immune diseases.
Results:
Multiomic analyses revealed that KIT+ ILC2s maintain a unique hybrid character marked by expression and open chromatin of genes linked to both ILC progenitors and ILC2 biology. KIT+ ILC2s showed extensive epigenomic priming at gene loci related to naive lymphocyte biology, tissue homing, and ILC3 effector functions, including IL17 and IL23R-explaining why KIT+ ILC2s are poised to adopt an ILC3-like phenotype. Genetic risk variants for asthma and autoimmunity are enriched in the poised epigenome of KIT+ ILC2s. Common γ-chain cytokines IL-2/IL-7 induced and maintained a KIT+ phenotype in KITneg ILC2s through STAT5 activation.
Conclusions:
Our study defines KIT+ ILC2s as existing in a developmentally immature state and carrying a precursor-like epigenome that promotes phenotypic plasticity and is linked to immune disease susceptibility. Importantly, we identify STAT5-mediated cytokine signals as candidates for therapeutic targeting of KIT+ ILC2s.
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