Interleukin 4 promotes the development of ex-Foxp3 Th2 cells during immunity to intestinal helminths

VS Pelly, SM Coomes, Y Kannan, M Gialitakis… - Journal of Experimental …, 2017 - rupress.org
VS Pelly, SM Coomes, Y Kannan, M Gialitakis, LJ Entwistle, J Perez-Lloret, S Czieso…
Journal of Experimental Medicine, 2017rupress.org
Immunity to intestinal helminth infections requires the rapid activation of T helper 2 cells (Th2
cells). However, simultaneous expansion of CD4+ Foxp3+ regulatory T cells (T reg cells)
impedes protective responses, resulting in chronic infections. The ratio between T reg and
effector T cells can therefore determine the outcome of infection. The redifferentiation of T
reg cells into Th cells has been identified in hyperinflammatory diseases. In this study, we
asked whether ex–T reg Th2 cells develop and contribute to type-2 immunity. Using …
Immunity to intestinal helminth infections requires the rapid activation of T helper 2 cells (Th2 cells). However, simultaneous expansion of CD4+Foxp3+ regulatory T cells (T reg cells) impedes protective responses, resulting in chronic infections. The ratio between T reg and effector T cells can therefore determine the outcome of infection. The redifferentiation of T reg cells into Th cells has been identified in hyperinflammatory diseases. In this study, we asked whether ex–T reg Th2 cells develop and contribute to type-2 immunity. Using multigene reporter and fate-reporter systems, we demonstrate that a significant proportion of Th2 cells derive from Foxp3+ cells after Heligmosomoides polygyrus infection and airway allergy. Ex-Foxp3 Th2 cells exhibit characteristic Th2 effector functions and provide immunity to H. polygyrus. Through selective deletion of Il4ra on Foxp3+ cells, we further demonstrate IL-4 is required for the development of ex-Foxp3 Th2 cells. Collectively, our findings indicate that converting T reg cells into Th2 cells could concomitantly enhance Th2 cells and limit T reg cell–mediated suppression.
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