Abstract:
: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.
journal_name
Immunityjournal_title
Immunityauthors
Wang Y,Bi Y,Chen X,Li C,Li Y,Zhang Z,Wang J,Lu Y,Yu Q,Su H,Yang H,Liu Gdoi
10.1016/j.immuni.2016.05.009subject
Has Abstractpub_date
2016-06-21 00:00:00pages
1337-49issue
6eissn
1074-7613issn
1097-4180pii
S1074-7613(16)30163-7journal_volume
44pub_type
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