Projects per year
Abstract
CD4+ T helper (Th) cell differentiation is controlled by lineage-specific expression of transcription factors and effector proteins, as well as silencing of lineage-promiscuous genes. Lysine methyltransferases (KMTs) comprise a major class of epigenetic enzymes that are emerging as important regulators of Th cell biology. Here, we show that the KMT DOT1L regulates Th cell function and lineage integrity. DOT1L-dependent dimethylation of lysine 79 of histone H3 (H3K79me2) is associated with lineage-specific gene expression. However, DOT1L-deficient Th cells overproduce IFN-γ under lineage-specific and lineage-promiscuous conditions. Consistent with the increased IFN-γ response, mice with a T-cell-specific deletion of DOT1L are susceptible to infection with the helminth parasite Trichuris muris and are resistant to the development of allergic lung inflammation. These results identify a central role for DOT1L in Th2 cell lineage commitment and stability and suggest that inhibition of DOT1L may provide a therapeutic strategy to limit type 2 immune responses.
Original language | English |
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Article number | 108505 |
Number of pages | 19 |
Journal | Cell Reports |
Volume | 33 |
Issue number | 11 |
DOIs | |
Publication status | Published - 15 Dec 2020 |
Keywords
- asthma
- CD4 T cells
- DOT1L
- IFN-γ
- Th1
- Th2
- Trichuris muris
Projects
- 2 Finished
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Epigenetic regulation of lymphoid cell development and function
National Health and Medical Research Council (NHMRC) (Australia)
1/01/15 → 31/12/18
Project: Research
Equipment
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Bioinformatics Platform
Deanna Deveson (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility
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FlowCore
Andrew Fryga (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility
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Micromon
Scott Coutts (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility