Study of the role of c-Maf in type 2 innate lymphoid cells

Group 2 innate lymphoid cells (ILC2s) are involved in type 2 inflammatory diseases such as allergy. In response to repeated allergen inhalations, lung epithelial cells secrete innate cytokines that activate ILC2s to release interleukin-5 (IL-5) and interleukin-13 (IL-13) resulting in eosinophil infiltration, mucus hyper-production, and airway hyperreactivity. Beside GATA3, very little is known about the role of specific transcription factors in the regulation of ILC2's function. Here we identify c-Maf as a crucial regulator of ILC2 function and identity. c-Maf deficient ILC2s are impaired in IL-5 and IL-13 production and eosinophil recruitment. Transcriptomic analysis underlined a reduced expression of genes associated with Th2/ILC2 identity and memory development that we confirmed both in mice and human, either in ILC2s engineered to express less c-Maf or in naturally c-Maflow ILC2s from cord blood. Our results indicate that c-Maf is a core node that connects immature to primed/trained ILC2s. Overall design: Study of WT and c-Maf-KO ILC2 after papain induced lung inflammation. ILC2 were sorted from lungs of mouse, either WT or c-Maf KO, 5 replicates were included for each genotype.