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

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dc.contributor.authorPelly, Victoria S
dc.contributor.authorGialitakis, Manolis
dc.contributor.authorOkoye, Isobel S
dc.contributor.authorRYckerl, Dominik
dc.contributor.authorAllen, Judith E
dc.contributor.authorBrombacher, Frank
dc.contributor.authorWilson, Mark S
dc.date.accessioned2021-10-08T07:22:57Z
dc.date.available2021-10-08T07:22:57Z
dc.date.issued2017
dc.description.abstractImmunity 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.
dc.identifier.apacitationPelly, V. S., Gialitakis, M., Okoye, I. S., RYckerl, D., Allen, J. E., Brombacher, F., & Wilson, M. S. (2017). Interleukin 4 promotes the development of ex-Foxp3 Th2 cells during immunity to intestinal helminths. <i>The Journal of Experimental Medicine</i>, 214(6), 1809 - 1826. http://hdl.handle.net/11427/35035en_ZA
dc.identifier.chicagocitationPelly, Victoria S, Manolis Gialitakis, Isobel S Okoye, Dominik RYckerl, Judith E Allen, Frank Brombacher, and Mark S Wilson "Interleukin 4 promotes the development of ex-Foxp3 Th2 cells during immunity to intestinal helminths." <i>The Journal of Experimental Medicine</i> 214, 6. (2017): 1809 - 1826. http://hdl.handle.net/11427/35035en_ZA
dc.identifier.citationPelly, V.S., Gialitakis, M., Okoye, I.S., RYckerl, D., Allen, J.E., Brombacher, F. & Wilson, M.S. 2017. Interleukin 4 promotes the development of ex-Foxp3 Th2 cells during immunity to intestinal helminths. <i>The Journal of Experimental Medicine.</i> 214(6):1809 - 1826. http://hdl.handle.net/11427/35035en_ZA
dc.identifier.issn0022-1007
dc.identifier.issn1540-9538
dc.identifier.ris TY - Journal Article AU - Pelly, Victoria S AU - Gialitakis, Manolis AU - Okoye, Isobel S AU - RYckerl, Dominik AU - Allen, Judith E AU - Brombacher, Frank AU - Wilson, Mark S AB - 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. DA - 2017 DB - OpenUCT DP - University of Cape Town IS - 6 J1 - The Journal of Experimental Medicine LK - https://open.uct.ac.za PY - 2017 SM - 0022-1007 SM - 1540-9538 T1 - Interleukin 4 promotes the development of ex-Foxp3 Th2 cells during immunity to intestinal helminths TI - Interleukin 4 promotes the development of ex-Foxp3 Th2 cells during immunity to intestinal helminths UR - http://hdl.handle.net/11427/35035 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/35035
dc.identifier.vancouvercitationPelly VS, Gialitakis M, Okoye IS, RYckerl D, Allen JE, Brombacher F, et al. Interleukin 4 promotes the development of ex-Foxp3 Th2 cells during immunity to intestinal helminths. The Journal of Experimental Medicine. 2017;214(6):1809 - 1826. http://hdl.handle.net/11427/35035.en_ZA
dc.language.isoeng
dc.publisher.departmentInternational Centre for Genetic Engineering and Biotechnology
dc.publisher.facultyFaculty of Health Sciences
dc.sourceThe Journal of Experimental Medicine
dc.source.journalissue6
dc.source.journalvolume214
dc.source.pagination1809 - 1826
dc.source.urihttps://dx.doi.org/10.1084/jem.20161104
dc.subject.otherAdoptive Transfer
dc.subject.otherAnimals
dc.subject.otherCell Polarity
dc.subject.otherForkhead Transcription Factors
dc.subject.otherGene Expression Profiling
dc.subject.otherImmunity
dc.subject.otherInterleukin-4
dc.subject.otherIntestines
dc.subject.otherMice, Inbred C57BL
dc.subject.otherNematospiroides dubius
dc.subject.otherReceptors, Interleukin-4
dc.subject.otherSignal Transduction
dc.subject.otherStrongylida Infections
dc.subject.otherT-Lymphocytes, Regulatory
dc.titleInterleukin 4 promotes the development of ex-Foxp3 Th2 cells during immunity to intestinal helminths
dc.typeJournal Article
uct.type.publicationResearch
uct.type.resourceJournal Article
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