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Cortisol synergizing with endoplasmic reticulum stress induces regulatory T-cell dysfunction
Jiangping Luo1, Caijie Zhou2, Shiqi Wang3,4,5,6,7
1Department of Chinese Traditional Medicine, Third Affiliated Hospital of Shenzhen University, Shenzhen, China.
Immunology
|July 21, 2023
Summary
Cortisol and endoplasmic reticulum (ER) stress impair regulatory T cell (Treg) function in food allergy by increasing Rnf20. Inhibiting Rnf20 restores Treg function and alleviates allergy symptoms in mice.
Area of Science:
- Immunology
- Endocrinology
- Molecular Biology
Background:
- Regulatory T cells (Tregs) are crucial for immune homeostasis and preventing autoimmune diseases.
- Dysfunctional Tregs are implicated in the pathogenesis of various immune disorders, including food allergy (FA).
- Current therapeutic strategies to restore Treg function are insufficient, necessitating novel approaches.
Purpose of the Study:
- To investigate the combined impact of cortisol and endoplasmic reticulum (ER) stress on Treg function in food allergy.
- To identify molecular mechanisms underlying Treg dysfunction in FA.
- To explore potential therapeutic targets for restoring Treg function in FA.
Main Methods:
- Analysis of serum cortisol and Treg counts in food allergy patients.
- Induction of ER stress in Tregs from FA patients and a mouse model of FA.
- Assessment of Treg suppressive function and molecular markers (Rnf20, Foxp3, TGF-β).
- Evaluation of Rnf20 inhibition in vitro and in vivo models of FA.
Main Results:
- FA patients exhibited elevated cortisol levels and ER stress in Tregs, negatively correlating with Treg counts.
- Cortisol exacerbated ER stress-induced Treg dysfunction.
- Cortisol and antigen-specific immune response induced Rnf20 expression in Tregs.
- Rnf20 suppressed Treg function by reducing Foxp3 and TGF-β expression.
- Rnf20 inhibition restored Treg suppressive function in FA patients and attenuated FA in mice.
Conclusions:
- Synergistic action of cortisol and ER stress impairs Treg function in FA via Rnf20 induction.
- Rnf20 acts as a key mediator in Treg dysfunction by downregulating Foxp3 and TGF-β.
- Targeting Rnf20 presents a promising therapeutic strategy for restoring Treg function and treating FA.
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