JCI insight · 2020
Th17 reprogramming of T cells in systemic juvenile idiopathic arthritis.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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История · было → стало
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Henderson Lauren A, Hoyt Kacie J, Lee Pui Y, Rao Deepak A, Jonsson A Helena, Nguyen Jennifer P, Rutherford Kayleigh, Julé Amélie M, Charbonnier Louis-Marie, Case Siobhan, Chang Margaret H, Cohen Ezra M, Dedeoglu Fatma, Fuhlbrigge Robert C, Halyabar Olha, Hazen Melissa M, Janssen Erin, Kim Susan, Lo Jeffrey, Lo Mindy S, Meidan Esra, Son Mary Beth F, Sundel Robert P, Stoll Matthew L, Nusbaum Chad, Lederer James A, Chatila Talal A, Nigrovic Peter A
Аннотация
Systemic juvenile idiopathic arthritis (sJIA) begins with fever, rash, and high-grade systemic inflammation but commonly progresses to a persistent afebrile arthritis. The basis for this transition is unknown. To evaluate a role for lymphocyte polarization, we characterized T cells from patients with acute and chronic sJIA using flow cytometry, mass cytometry, and RNA sequencing. Acute and chronic sJIA each featured an expanded population of activated Tregs uncommon in healthy controls or in children with nonsystemic JIA. In acute sJIA, Tregs expressed IL-17A and a gene expression signature reflecting Th17 polarization. In chronic sJIA, the Th17 transcriptional signature was identified in T effector cells (Teffs), although expression of IL-17A at the protein level remained rare. Th17 polarization was abrogated in patients responding to IL-1 blockade. These findings identify evolving Th17 polarization in sJIA that begins in Tregs and progresses to Teffs, likely reflecting the impact of the cytokine milieu and consistent with a biphasic model of disease pathogenesis. The results support T cells as a potential treatment target in sJIA.