Related Experiment Video
Updated: Apr 16, 2026

Study of Dendritic Cell Development by Short Hairpin RNA-Mediated Gene Knockdown in a Hematopoietic Stem and Progenitor Cell Line In vitro
Published on: March 7, 2022
Dendritic cell SIRT1-HIF1α axis programs the differentiation of CD4+ T cells through IL-12 and TGF-β1
Guangwei Liu1, Yujing Bi2, Lixiang Xue3
1Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Biotherapy Research Center and Institute of Immunobiology, Fudan University, Shanghai 200032, China; liugw@fudan.edu.cn ruoning.wang@nationwidechildren.org.
Abstract:
The differentiation of naive CD4(+) T cells into distinct lineages plays critical roles in mediating adaptive immunity or maintaining immune tolerance. In addition to being a first line of defense, the innate immune system also actively instructs adaptive immunity through antigen presentation and immunoregulatory cytokine production. Here we found that sirtuin 1 (SIRT1), a type III histone deacetylase, plays an essential role in mediating proinflammatory signaling in dendritic cells (DCs), consequentially modulating the balance of proinflammatory T helper type 1 (TH1) cells and antiinflammatory Foxp3(+) regulatory T cells (T(reg) cells). Genetic deletion of SIRT1 in DCs restrained the generation of T(reg) cells while driving TH1 development, resulting in an enhanced T-cell-mediated inflammation against microbial responses. Beyond this finding, SIRT1 signaled through a hypoxia-inducible factor-1 alpha (HIF1α)-dependent pathway, orchestrating the reciprocal TH1 and T(reg) lineage commitment through DC-derived IL-12 and TGF-β1. Our studies implicates a DC-based SIRT1-HIF1α metabolic checkpoint in controlling T-cell lineage specification.
Related Concept Videos
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
B Cell Activation and Differentiation
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
TGF - β Signaling Pathway

