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

PLoS One. 2014 Sep 25;9(9):e108649. doi: 10.1371/journal.pone.0108649. eCollection 2014.

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cytokines / metabolism
  • Female
  • Filariasis / genetics*
  • Filariasis / immunology*
  • Gene Expression Profiling
  • Homeostasis* / genetics
  • Homeostasis* / immunology
  • Humans
  • Immunity, Innate*
  • Lymphocyte Count
  • Lymphocytes / immunology*
  • Lymphocytes / metabolism*
  • Male
  • MicroRNAs / genetics
  • Middle Aged
  • Models, Biological
  • Proto-Oncogene Proteins c-kit / metabolism*
  • Signal Transduction
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Transcription, Genetic
  • Transcriptome*
  • Young Adult

Substances

  • Cytokines
  • MicroRNAs
  • Proto-Oncogene Proteins c-kit