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

Autor:	Pelly VS; Allergy and Anti-Helminth Immunity Laboratory, Mill Hill Laboratory, The Francis Crick Institute, London NW7 1AA, England, UK., Coomes SM; Allergy and Anti-Helminth Immunity Laboratory, Mill Hill Laboratory, The Francis Crick Institute, London NW7 1AA, England, UK., Kannan Y; Allergy and Anti-Helminth Immunity Laboratory, Mill Hill Laboratory, The Francis Crick Institute, London NW7 1AA, England, UK., Gialitakis M; Ahr Immunity Laboratory, Mill Hill Laboratory, The Francis Crick Institute, London NW7 1AA, England, UK., Entwistle LJ; Allergy and Anti-Helminth Immunity Laboratory, Mill Hill Laboratory, The Francis Crick Institute, London NW7 1AA, England, UK., Perez-Lloret J; Allergy and Anti-Helminth Immunity Laboratory, Mill Hill Laboratory, The Francis Crick Institute, London NW7 1AA, England, UK., Czieso S; Allergy and Anti-Helminth Immunity Laboratory, Mill Hill Laboratory, The Francis Crick Institute, London NW7 1AA, England, UK., Okoye IS; Allergy and Anti-Helminth Immunity Laboratory, Mill Hill Laboratory, The Francis Crick Institute, London NW7 1AA, England, UK., Rückerl D; Faculty of Life Sciences (3IR), University of Manchester, Manchester M13 9PT, England, UK., Allen JE; Faculty of Life Sciences (3IR), University of Manchester, Manchester M13 9PT, England, UK., Brombacher F; International Centre for Genetic Engineering and Biotechnology, University of Cape Town, Institute of Infectious Disease and Molecular Medicine and South African Medical Research Council, 7925 Cape Town, South Africa., Wilson MS; Allergy and Anti-Helminth Immunity Laboratory, Mill Hill Laboratory, The Francis Crick Institute, London NW7 1AA, England, UK wilson.mark@gene.com.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2017 Jun 05; Vol. 214 (6), pp. 1809-1826. Date of Electronic Publication: 2017 May 15.
DOI:	10.1084/jem.20161104
Abstrakt:	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. (© 2017 Pelly et al.)
Databáze:	MEDLINE
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