Aryl hydrocarbon receptor (AhR) is a key transcription factor that modulates the differentiation of T helper 17 (Th17) cells. How AhR is regulated at the post-translational level in Th17 cells remains largely unclear. Here we identify USP21 as a newly defined deubiquitinase of AhR. We demonstrate that USP21 interacts with and stabilizes AhR by removing the K48-linked polyubiquitin chains from AhR. Interestingly, USP21 inhibits the transcriptional activity of AhR in a deubiquitinating-dependent manner. USP21 deubiquitinates AhR at the K432 residue, and the maintenance of ubiquitination on this site is required for the intact transcriptional activity of AhR. Moreover, the deficiency of USP21 promotes the differentiation of Th17 cells both in vitro and in vivo. Consistently, adoptive transfer of USP21 deficient naïve CD4+ T cells elicits more severe colitis in Rag1-/- recipients. Therefore, our study reveals a novel mechanism in which USP21 deubiquitinates AhR and negatively regulates the differentiation of Th17 cells.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/jleuko/qiae148 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Th17 and effector CD8 T cells relate to disease progression in amyotrophic lateral sclerosis: a case control study.
J Neuroinflammation
December 2024
Department of Neurology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
The immune system has garnered attention due to its association with disease progression in amyotrophic lateral sclerosis (ALS). However, the role of peripheral immune cells in this context remains controversial. Here, we conducted single-cell RNA-sequencing of peripheral blood mononuclear cells to comprehensively profile immune cells concerning the rate of disease progression in patients with ALS.
View Article and Find Full Text PDFAP-1 activates KCNN4-mediated Ca2 signaling to induce the Th1/Th17 differentiation of CD4 cells in chronic non-bacterial prostatitis.
Cell Biol Toxicol
December 2024
Department of Urology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100700, P.R. China.
The intraprostatic inflammatory infiltrate is characterized by Th1 CD4 T cells, and its molecular mechanism is not well defined. This study explored the mechanisms responsible for the alteration of Th1/Th17 differentiation of CD4 T cells in chronic non-bacterial prostatitis (CNP). CNP rats were induced by the administration of testosterone and 17β-estradiol.
View Article and Find Full Text PDFImmune imbalance in Lupus Nephritis: The intersection of T-Cell and ferroptosis.
Front Immunol
December 2024
School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Deyang Hospital Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Deyang, China.
Ferroptosis is a novel form of cell death characterized by unlimited accumulation of iron-dependent lipid peroxides. It is often accompanied by disease, and the relationship between ferroptosis of immune cells and immune regulation has been attracting increasing attention. Initially, it was found in cancer research that the inhibition of regulatory T cell (Treg) ferroptosis and the promotion of CD8+ T cell ferroptosis jointly promoted the formation of an immune-tolerant environment in tumors.
View Article and Find Full Text PDFHyperbaric Oxygen Protects Acute Lung Injury Secondary to Venom Poisoning by Regulating Th17/Treg Balance.
Discov Med
December 2024
Emergency Department, Affiliated Hospital of Zunyi Medical University, 563000 Zunyi, Guizhou, China.
Background: To explore the mechanism of hyperbaric oxygen (HBO) intervention on acute lung injury secondary to snake venom poisoning and provide more toxicological and clinical evidence for venom poisoning.
Methods: Male Kunming mice (n = 96) were randomly divided into four groups: the control group which was not given any interventional treatments, venom group in which each mouse was injected with venom (1 mg/kg) through the tail vein, antivenom group in which each mouse was injected with anti- venom immediately after the model was successfully established, and HBO+antivenom group in which each mouse was given HBO treatment at 1 h, 5 h, 11 h and 23 h following the injection of antivenom. Lung tissues of mice were obtained and processed for the detection of the lung coefficient, the levels of inflammatory factors such as interleukin (IL)-6, IL-10 and IL-17, and the protein expression of retinoic acid receptor (RAR)-related orphan receptor gamma (RORγt) and forkhead box P3 (FOXP3).
CBL/Cbl-b mediates Fas degradation to reduce neuronal damage in experimental autoimmune encephalomyelitis.
Scand J Immunol
January 2025
Department of Neurology, the Second Clinical Medical College, Henan University of Traditional Chinese Medicine, Zhengzhou, China.
Fas has been shown to positively regulate the differentiation of T helper 17 (Th17) cells in mouse models of experimental autoimmune encephalomyelitis (EAE). Fas protein expression is regulated by ubiquitination but has not been further studied. In this study, we investigated the role of the Fas ubiquitin ligase in Th17 cell differentiation and highlighted its potential as a therapeutic target for EAE.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!