title: 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.
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Alexis
authors.initials: A
authors.lastname: Boyd
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: José M C
authors.initials: JM
authors.lastname: Ribeiro
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005368:Filariasis / Q000235:genetics* / Q000276:immunology*; D020869:Gene Expression Profiling; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D008954:Models, Biological; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic; D059467:Transcriptome; D055815:Young Adult
chemical_list: D016207:Cytokines; D035683:MicroRNAs; D019009:Proto-Oncogene Proteins c-kit