Th memory for interleukin‐17 expression is stable in vivo

MH Lexberg, A Taubner, A Förster… - European journal of …, 2008 - Wiley Online Library
MH Lexberg, A Taubner, A Förster, I Albrecht, A Richter, T Kamradt, A Radbruch, HD Chang
European journal of immunology, 2008Wiley Online Library
Based on the memory for the re‐expression of certain cytokine genes, different subsets of Th
cells have been defined. In Th type 1 (Th1) and Th2 memory lymphocytes, the genes for the
cytokines interferon‐γ and interleukin (IL)‐4 are imprinted for expression upon restimulation
by the expression of the transcription factors T‐bet and GATA‐3, respectively, and
epigenetic modification of the cytokine genes. In Th17 cells, IL‐17 expression is dependent
on the transcription factors RORγt and RORα. Here, we analyze the stability and plasticity of …
Abstract
Based on the memory for the re‐expression of certain cytokine genes, different subsets of Th cells have been defined. In Th type 1 (Th1) and Th2 memory lymphocytes, the genes for the cytokines interferon‐γ and interleukin (IL)‐4 are imprinted for expression upon restimulation by the expression of the transcription factors T‐bet and GATA‐3, respectively, and epigenetic modification of the cytokine genes. In Th17 cells, IL‐17 expression is dependent on the transcription factors RORγt and RORα. Here, we analyze the stability and plasticity of IL‐17 memory in Th17 cells. We have developed a cytometric IL‐17 secretion assay for the isolation of viable Th cells secreting IL‐17. For Th17 cells generated in vitro, IL‐17 expression itself is dependent on continued TGF‐β/IL‐6 or IL‐23 signaling and is blocked by interferon‐γ and IL‐4 signaling. In response to IL‐12 and IL‐4, in vitro generated Th17 cells are converted into Th1 or Th2 cells, respectively. Th17 cells isolated ex vivo, however, maintain their IL‐17 memory upon subsequent in vitro culture, even in the absence of IL‐23. Their cytokine memory is not regulated by IL‐12 or IL‐4. Th17 cells generated in vivo are a stable and distinct lineage of Th cell differentiation.
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