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Immunol."],"abstract":"<jats:p>In juvenile idiopathic arthritis (JIA) inflammatory T cells and their produced cytokines are drug targets and play a role in disease pathogenesis. Despite their clinical importance, the sources and types of inflammatory T cells involved remain unclear. T cells respond to polarizing factors to initiate types of immunity to fight infections, which include immunity types 1 (T1), 2 (T2), and 3 (T17). Polarizing factors drive CD4<jats:sup>+<\/jats:sup> T cells towards T helper (Th) cell subtypes and CD8<jats:sup>+<\/jats:sup> T cells towards cytotoxic T cell (Tc) subtypes. T1 and T17 polarization are associated with autoimmunity and production of the cytokines IFN\u03b3 and IL-17 respectively. We show that JIA and child healthy control (HC) peripheral blood mononuclear cells are remarkably similar, with the same frequencies of CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> na\u00efve and memory T cell subsets, T cell proliferation, and CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cell subsets upon T1, T2, and T17 polarization. Yet, under T1 polarizing conditions JIA cells produced increased IFN\u03b3 and inappropriately produced IL-17. Under T17 polarizing conditions JIA T cells produced increased IL-17. Gene expression of IFN\u03b3, IL-17, Tbet, and ROR\u03b3T by quantitative PCR and RNA sequencing revealed activation of immune responses and inappropriate activation of IL-17 signaling pathways in JIA polarized T1 cells. The polarized JIA T1 cells were comprised of Th and Tc cells, with Th cells producing IFN\u03b3 (Th1), IL-17 (Th17), and both IFN\u03b3-IL-17 (Th1.17) and Tc cells producing IFN\u03b3 (Tc1). The JIA polarized CD4<jats:sup>+<\/jats:sup> T1 cells expressed both Tbet and ROR\u03b3T, with higher expression of the transcription factors associated with higher frequency of IL-17 producing cells. T1 polarized na\u00efve CD4<jats:sup>+<\/jats:sup> cells from JIA also produced more IFN\u03b3 and more IL-17 than HC. We show that in JIA T1 polarization inappropriately generates Th1, Th17, and Th1.17 cells. Our data provides a tool for studying the development of heterogeneous inflammatory T cells in JIA under T1 polarizing conditions and for identifying pathogenic immune cells that are important as drug targets and diagnostic markers.<\/jats:p>","DOI":"10.3389\/fimmu.2022.848168","type":"journal-article","created":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T15:55:13Z","timestamp":1656950113000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Increased Development of Th1, Th17, and Th1.17 Cells Under T1 Polarizing Conditions in Juvenile Idiopathic Arthritis"],"prefix":"10.3389","volume":"13","author":[{"given":"Anna 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