Th17 cells demonstrate stable cytokine production in allergic inflammation (P1143)

Abstract

Abstract Th17 cells are critical for the clearance of extracellular bacteria and fungi, but also contribute to the pathology of autoimmune diseases and asthma. Th17 cells can acquire a Th1-like phenotype in vitro and in vivo, but less is known about their ability to adopt Th2 and Th9 effector programs. To explore this in more detail, we generated an IL-17F lineage tracer mouse strain that allows tracking of cells that formerly expressed IL-17F and can be used to test stability of the Th17 phenotype. Th17 cells cultured under polarizing conditions that promote Th1, Th2 or Th9 differentiation adopt the respective effector programs, expressing lineage associated transcription factors, and secreting IFN-γ, IL-4 or IL-9, while diminishing IL-17 production and expression of RORγt. To explore the stability of Th17 cells in an in vivo environment that is associated with the development of Th2 and Th9 cells, we used the adjuvant-dependent, OVA/Alum and the adjuvant-free, house dust mite models of allergic airway disease (AAD). In both models of AAD, Th17 cells from the lungs of diseased mice did not secrete alternative cytokines nor adopt Th1, Th2 or Th9 effector programs, but remained stable IL-17-secretors. Thus, although Th1-biased pro-inflammatory environments have been shown to induce alternative cytokine expression from Th17 cells in vivo, our data suggest that during allergic inflammatory disease, Th17 cells are remarkably stable, and retain the potential to produce IL-17.