Interleukin 4 promotes the development of ex-Foxp3 Th2 cells during immunity to intestinal helminths
journal contributionposted on 2020-10-15, 16:30 authored by Victoria S Pelly, Stephanie M Coomes, Yashaswini Kannan, Manolis Gialitakis, Lewis J Entwistle, Jimena Perez-Lloret, Stephanie Czieso, Isobel S Okoye, Dominik Rückerl, Judith E Allen, Frank Brombacher, Mark S Wilson
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.
Adoptive TransferAnimalsCell PolarityForkhead Transcription FactorsGene Expression ProfilingImmunityInterleukin-4IntestinesMice, Inbred C57BLNematospiroides dubiusReceptors, Interleukin-4Signal TransductionStrongylida InfectionsT-Lymphocytes, RegulatoryTh2 CellsWilson FC001220Stockinger FC001159FC-ackBRF-ackHP-ackAS-ackImmunology11 Medical and Health Sciences