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SP0109 Twisting pathogenic T cell memory
  1. A. Radbruch
  1. Cell Biology, DRFZ, Berlin, Germany


Proinflammatory T helper (Th) lymphocytes initiate and presumably also drive chronic inflammation. It is unclear, however, how they escape physiological and therapeutic immunregulation, persist and adapt to the inflammatory environment. To understand the molecular mechanisms underlying the transition of an acute self-limiting T cell response to a chronic pathogenic effector/memory response, the genes regulating these processes have to be identified. To this end, and with the rationale that Th cells driving chronic inflammation have a history of repeated encounter with (self)antigen, the global gene expression signature of Th cells of the Th1, Th2 and Th17 lineages was compared, activated just once or repeatedly reactivated. The genes Twist1 and Hopx are upregulated selectively in proinflammatory Th1 cells upon repeated restimulation. Twist1 encodes an E-box binding transcription factor and is highly expressed in Th cells of inflamed tissue of patients with rheumatic or gastrointestinal inflammation. Knock-down of Twist1 in Th1 cells of murine models of arthritis exacerbates chronic inflammation, but also regulates genes controlling survival and apoptosis. Hopx promotes the survival of Th1 cells. ShRNA-mediated downregulation of Hopx in Th1 cells reduces their ability to persist in vivo, following adoptive transfer. Th1 cells lacking Hopx do not induce inflammation in experimental colitis or arthritis. Thus, Twist1 and Hopx qualify as markers of Th1 cells in chronic inflammation, reflect molecular adaptation to chronicity, regulate function and persistence of Th1 cells, and may allow to target therapies selectively to pathogenic versus protective Th cells.

Disclosure of Interest None Declared

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