Blocking the aryl hydrocarbon receptor (AhR) protects CD4+ T cells from Th17/Treg differentiation imbalance through SENP1-mediated deSUMOylation.

Authors

Jiao Ge, Yan Liu

Published in

Human immunology. Volume 87. Issue 9. Pages 111811. Jul 17, 2026. Epub Jul 17, 2026.

Abstract

Immune thrombocytopenic purpura (ITP) is the most common autoimmune bleeding disorder in children and poses a serious threat to pediatric health and survival. An imbalance in Th17 and Treg cell differentiation leads to uncontrolled inflammation.
Peripheral blood mononuclear cells and CD4⁺ T cells were isolated from 23 ITP patients and 23 healthy controls. Th17 and Treg proportions were quantified by flow cytometry, and serum concentrations of IL-17 A, IL-10, IL-22, IL-23, IL-6, and TNF-α were measured by ELISA. An ITP mouse model was established by splenocyte transfer, and AhR antagonism was evaluated using CH-223191. AhR SUMOylation was assessed by co-immunoprecipitation and western blot, and transcriptional activity was determined by dual-luciferase reporter assay.
The Th17/Treg ratio was significantly elevated in ITP patients compared with controls (P < 0.001), accompanied by increased serum IL-17 A, IL-22, IL-23, IL-6, and TNF-α and decreased IL-10 (P < 0.001). AhR mRNA and protein expression were markedly upregulated in ITP CD4⁺ T cells (P < 0.001). Inhibition of AhR by CH-223191 reduced the Th17 proportion from 3.5% to 2.0% and increased the Treg proportion from 1.2% to 2.8%, normalizing the Th17/Treg ratio (P < 0.001). Consistent results were observed in vivo, with improved platelet counts and restored Th17/Treg balance. Mechanistically, AhR underwent SUMOylation at K63 and K510 by SUMO1, which enhanced AhR protein stability and transcriptional activity; this modification was reversed by SENP1-mediated deSUMOylation.
Blocking AhR, which is modified by SUMO1 and deSUMOylated by SENP1, alleviates ITP-induced Th17/Treg imbalance through SENP1-mediated deSUMOylation.

PMID:
42468071
Bibliographic data and abstract were imported from PubMed on 18 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.