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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2023

Open Access 01-12-2023 | Uveitis | Research

Progesterone attenuates Th17-cell pathogenicity in autoimmune uveitis via Id2/Pim1 axis

Authors: Xiuxing Liu, Chenyang Gu, Jianjie Lv, Qi Jiang, Wen Ding, Zhaohao Huang, Yidan Liu, Yuhan Su, Chun Zhang, Zhuping Xu, Xianggui Wang, Wenru Su

Published in: Journal of Neuroinflammation | Issue 1/2023

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Abstract

Background

Autoimmune uveitis (AU) is the most common ophthalmic autoimmune disease (AD) and is characterized by a complex etiology, high morbidity, and high rate of blindness. AU remission has been observed in pregnant female patients. However, the effects of progesterone (PRG), a critical hormone for reproduction, on the treatment of AU and the regulatory mechanisms remain unclear.

Methods

To this end, we established experimental autoimmune uveitis (EAU) animal models and constructed a high-dimensional immune atlas of EAU-model mice undergoing PRG treatment to explore the underlying therapeutic mechanisms of PRG using single-cell RNA sequencing.

Results

We found that PRG ameliorated retinal lesions and inflammatory infiltration in EAU-model mice. Further single-cell analysis indicated that PRG reversed the EAU-induced expression of inflammatory genes (AP-1 family, S100a family, and Cxcr4) and pathological processes related to inflammatory cell migration, activation, and differentiation. Notably, PRG was found to regulate the Th17/Treg imbalance by increasing the reduced regulatory functional mediators of Tregs and diminishing the overactivation of pathological Th17 cells. Moreover, the Id2/Pim1 axis, IL-23/Th17/GM-CSF signaling, and enhanced Th17 pathogenicity during EAU were reversed by PRG treatment, resulting in the alleviation of EAU inflammation and treatment of AD.

Conclusions

Our study provides a comprehensive single-cell map of the immunomodulatory effects of PRG therapy on EAU and elaborates on the possible therapeutic mechanisms, providing novel insights into its application for treating autoimmune diseases.
Appendix
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Metadata
Title
Progesterone attenuates Th17-cell pathogenicity in autoimmune uveitis via Id2/Pim1 axis
Authors
Xiuxing Liu
Chenyang Gu
Jianjie Lv
Qi Jiang
Wen Ding
Zhaohao Huang
Yidan Liu
Yuhan Su
Chun Zhang
Zhuping Xu
Xianggui Wang
Wenru Su
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2023
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-023-02829-3

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