Related Experiment Video
Updated: Jun 21, 2026
07:46
In Vitro Differentiation of Naive CD4+ T Cells into Pathogenic Th17 Cells in Mouse
Published on: October 25, 2024
The AP-1 transcription factor Batf controls T(H)17 differentiation
Barbara U Schraml1, Kai Hildner, Wataru Ise
1Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, Saint Louis, Missouri 63110, USA.
Nature
|July 7, 2009
Summary
The transcription factor BATF is essential for the development of T helper 17 (T(H)17) cells, which are crucial for host defense and implicated in autoimmune diseases. Loss of BATF impairs T(H)17 differentiation and protects against experimental autoimmune encephalomyelitis.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Activator protein 1 (AP-1) transcription factors regulate gene expression through dimerization.
- BATF, a member of the AP-1 family, lacks a canonical activation domain and was previously thought to inhibit AP-1 activity.
- T helper 17 (T(H)17) cells are critical for immunity but also involved in autoimmune pathogenesis.
Purpose of the Study:
- To investigate the role of the AP-1 transcription factor BATF in T(H)17 cell differentiation.
- To elucidate the molecular mechanisms by which BATF influences T(H)17 cell development and function.
Main Methods:
- Analysis of T(H)17 cell differentiation in Batf-deficient mice.
- Assessment of T(H)1 and T(H)2 cell differentiation.
- Investigation of gene expression related to T(H)17 differentiation (e.g., RORgamma t, IL21).
- Chromatin immunoprecipitation (ChIP) to determine BATF binding sites on target gene promoters and intergenic elements.
Main Results:
- Batf(-/-) mice exhibit normal T(H)1 and T(H)2 differentiation but a significant defect in T(H)17 cell differentiation.
- Batf(-/-) T cells fail to induce key factors like RORgamma t and IL21 necessary for T(H)17 development.
- Overexpression of IL21 or RORgamma t did not fully rescue IL17 production in Batf(-/-) T cells.
- BATF directly binds to the promoters of Il17, Il21, and Il22, as well as conserved intergenic elements within the Il17a-Il17f locus.
Conclusions:
- BATF is indispensable for T(H)17 cell differentiation.
- BATF acts as a critical regulator of T(H)17 cell identity and function.
- The findings reveal a novel, essential role for BATF in orchestrating the inflammatory response mediated by T(H)17 cells.
Related Concept Videos
01:30General Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
02:16Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
01:24T Cell Types and Functions
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
01:16TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
02:23Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
01:24B Cell Activation and Differentiation
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
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...
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...