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

Pelly, Victoria S; Gialitakis, Manolis; Okoye, Isobel S; RYckerl, Dominik; Allen, Judith E; Brombacher, Frank; Wilson, Mark S

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

Journal Article

2017

Journal Title

The Journal of Experimental Medicine

Link to Journal

https://dx.doi.org/10.1084/jem.20161104

Department

International Centre for Genetic Engineering and Biotechnology

Faculty

Faculty of Health Sciences

Abstract

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.