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Bcl11b is essential for licensing Th2 differentiation during helminth infection and allergic asthma

Author

Listed:
  • Kyle J. Lorentsen

    (University of Florida)

  • Jonathan J. Cho

    (University of Florida
    University of Florida College of Medicine)

  • Xiaoping Luo

    (University of Florida
    University of Florida College of Medicine)

  • Ashley N. Zuniga

    (University of Florida
    University of Florida College of Medicine)

  • Joseph F. Urban

    (US Department of Agriculture)

  • Liang Zhou

    (University of Florida
    University of Florida)

  • Raad Gharaibeh

    (University of Florida
    University of Florida)

  • Christian Jobin

    (University of Florida
    University of Florida)

  • Michael P. Kladde

    (University of Florida
    University of Florida)

  • Dorina Avram

    (University of Florida
    University of Florida College of Medicine
    University of Florida)

Abstract

During helminth infection and allergic asthma, naive CD4+ T-cells differentiate into cytokine-producing Type-2 helper (Th2) cells that resolve the infection or induce asthma-associated pathology. Mechanisms regulating the Th2 differentiation in vivo remain poorly understood. Here we report that mice lacking Bcl11b in mature T-cells have a diminished capacity to mount Th2 responses during helminth infection and allergic asthma, showing reduced Th2 cytokines and Gata3, and elevated Runx3. We provide evidence that Bcl11b is required to maintain chromatin accessibility at Th2-cytokine promoters and locus-control regions, and binds the Il4 HS IV silencer, reducing its accessibility. Bcl11b also binds Gata3-intronic and downstream-noncoding sites, sustaining the Gata3 expression. In addition, Bcl11b binds and deactivates upstream enhancers at Runx3 locus, restricting the Runx3 expression and its availability to act at the Il4 HS IV silencer. Thus, our results establish novel roles for Bcl11b in the regulatory loop that licenses Th2 program in vivo.

Suggested Citation

  • Kyle J. Lorentsen & Jonathan J. Cho & Xiaoping Luo & Ashley N. Zuniga & Joseph F. Urban & Liang Zhou & Raad Gharaibeh & Christian Jobin & Michael P. Kladde & Dorina Avram, 2018. "Bcl11b is essential for licensing Th2 differentiation during helminth infection and allergic asthma," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04111-0
    DOI: 10.1038/s41467-018-04111-0
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