Transcriptional regulation of type 2 innate lymphoid cells and precursors by interleukin-7 receptor signalling

Abstract

Abstract Innate lymphoid cells (ILCs) are a rare population of innate immune cells that act as the first line of defense against pathogens. These cells arise from the lymphoid lineage that B and T cells also belong to. Type 2 ILCs (ILC2s) are a subset of ILCs that reside in the lungs, mucosal layers, and skin, and have roles in clearing helminth infections, triggering allergic responses, and promoting lung tissue repair after influenza infections. The functions of ILC2s mirror those of TH2 cells but lack antigen recognition. However, their full development background is still unknown. It is believed that ILC2s develop in the fetal liver and adult bone marrow from common lymphoid progenitors and differentiate into several intermediates including helper ILC precursors. From this, ILC2 progenitors arise and express interleukin-7 (IL-7) receptor with the aid of the transcription factor GATA3. Our lab has found that IL-7 is critical for ILC2 development as mutations to the IL-7 receptor show a reduction in the ILC2 numbers and GATA3 expression. Conversely, overexpression of IL-7 results in the expansion of ILC2s and elevated GATA3 expression. We hypothesize that IL-7 signalling dictates ILC2 development through the transcriptional regulation of lineage determining factors. We aim to identify the transcriptional and epigenetic landscape regulated by IL-7 in ILC2s and their progenitors using single cell RNA sequencing and chromatin immunoprecipitation sequencing. We will also investigate how IL-7 influences airway immune responses generated by ILC2s using flow cytometry and RNA sequencing. This study will increase our understanding of a vital cell population and contribute to the development of therapeutics for allergic asthma and viral infections.