JIA patient T cells differentiate into Th1, Th17 and Th1.17 effector cells under Th1 polarizing conditions

ObjectiveT helper cells develop into discrete Th1, Th2 or Th17 lineages that selectively express IFN{gamma}, IL-4/IL-5/IL-13, or IL-17, respectively and actively silence signature cytokines expressed by opposing lineages. Our objective was to compare Th1, Th2 and Th17 polarization in cell culture models using JIA patient samples. MethodsPeripheral blood mononuclear cells were isolated from JIA or healthy prepubescent children. T cell naive and memory phenotypes were assessed by flow cytometry. T cell proliferation was measured using a fluorescence-based assay. Th cell cultures were generated in vitro and IFN{gamma}, IL-17, and TNF measured by ELISA and flow cytometry. ResultsJIA Th1 cells produced increased IFN{gamma} and inappropriately produced IL-17. JIA Th17 cells produced increased IL-17. JIA Th1 cell cultures develop dual producers of IFN{gamma} and IL-17, which are Th1.17 cells. JIA Th1 cultures expressed elevated levels of both T-bet and ROR{gamma}T. RNA sequencing confirmed activation of immune responses and inappropriate activation of IL-17 signaling pathways in Th1 cultures. A subset of JIA patient samples was disproportionally responsible for the enhanced IFN{gamma} and IL-17 phenotype and Th1.17 phenotype. ConclusionsThis study reveals that JIA patient uncommitted T cell precursors, but not healthy children, inappropriately develop into inflammatory effector Th1.17 and Th17 cells under Th1 polarizing conditions. Rheumatology key messagesO_LITh1 differentiation of JIA PBMCs generates high IFN{gamma}, IL-17, and dual IFN{gamma}-IL-17 producing cells. C_LIO_LIJIA Th1 differentiation increases master transcription factor expression for Tbet and ROR{gamma}T. C_LIO_LIEnhanced JIA Th1 IFN{gamma} and IL-17 production occurs in a subset of JIA patients. C_LI