Human CD117 (cKit)+ innate lymphoid cells have a discrete transcriptional profile at homeostasis and are expanded during filarial infection

Abstract

Since innate lymphoid cells (ILCs) have been found to play a role in the immune response to helminth parasites in rodents, we sought to determine their role in human helminth infection. By developing multicolor flow cytometry-based methods to identify and enumerate circulating ILCs and their subsets, we were able to identify a subset of cKit+ ILCs defined as Lineage (Lin)-/CD45+/cKit+/CD127+ that were significantly expanded in the filarial-infected individuals (p = 0.0473) as were those cKit+ ILCs that produced IL-13. Additionally, the frequency of these cKit+ ILCs correlated with the frequency of IL-17 producing CD4+T cells (Th17 cells; p = 0.025). To investigate the function of cKit+ ILCs, sorted, highly purified human ILCs were subjected to transcriptional profiling by RNAseq and compared to appropriate control cells. These cKit+ ILCs expressed TLRs, a broad range of cytokines/cytokine receptors and MHC Class II molecules suggesting that these ILCs sense pathogens independent of other cell types. Functional analysis revealed expanded cKit+ ILC-specific transcription and ILC-specific microRNA precursors.