[PDF][PDF] Histone deacetylase SIRT1 negatively regulates the differentiation of interleukin-9-producing CD4+ T cells
Immunity, 2016•cell.com
Distinct metabolic programs support the differentiation of CD4+ T cells into separate
functional subsets. In this study, we investigated metabolic mechanisms underlying the
differentiation of IL-9-producing CD4+ T cells (Th9) in allergic airway inflammation and
cancerous tumors. We found that histone deacetylase SIRT1 negatively regulated Th9 cell
differentiation. A deficiency of SIRT1 induced by either conditional deletion in mouse CD4+
T cells or the use of small interfering RNA (siRNA) in mouse or human T cells increased IL-9 …
functional subsets. In this study, we investigated metabolic mechanisms underlying the
differentiation of IL-9-producing CD4+ T cells (Th9) in allergic airway inflammation and
cancerous tumors. We found that histone deacetylase SIRT1 negatively regulated Th9 cell
differentiation. A deficiency of SIRT1 induced by either conditional deletion in mouse CD4+
T cells or the use of small interfering RNA (siRNA) in mouse or human T cells increased IL-9 …
Summary
Distinct metabolic programs support the differentiation of CD4+ T cells into separate functional subsets. In this study, we investigated metabolic mechanisms underlying the differentiation of IL-9-producing CD4+ T cells (Th9) in allergic airway inflammation and cancerous tumors. We found that histone deacetylase SIRT1 negatively regulated Th9 cell differentiation. A deficiency of SIRT1 induced by either conditional deletion in mouse CD4+ T cells or the use of small interfering RNA (siRNA) in mouse or human T cells increased IL-9 production, whereas ectopic SIRT1 expression inhibited it. Notably, SIRT1 inhibited Th9 cell differentiation that regulated anti-tumor immunity and allergic pulmonary inflammation. Glycolytic activation through the mTOR-hypoxia-inducible factor-1α (HIF1α) was required for the differentiation of Th9 cells that conferred protection against tumors and is involved in allergic airway inflammation. Our results define the essential features of SIRT1-mTOR-HIF1α signaling-coupled glycolytic pathway in inducing Th9 cell differentiation, with implications for metabolic reprogramming as an immunotherapeutic approach.
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