Progesterone attenuates Th17-cell pathogenicity in autoimmune uveitis via Id2/Pim1 axis
In: Journal of Neuroinflammation, Jg. 20 (2023), Heft 1, S. 1-19
Online
academicJournal
Zugriff:
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.
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Progesterone attenuates Th17-cell pathogenicity in autoimmune uveitis via Id2/Pim1 axis
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Autor/in / Beteiligte Person: | Liu, Xiuxing ; Gu, Chenyang ; Lv, Jianjie ; Jiang, Qi ; Ding, Wen ; Huang, Zhaohao ; Liu, Yidan ; Su, Yuhan ; Zhang, Chun ; Xu, Zhuping ; Wang, Xianggui ; Su, Wenru |
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Zeitschrift: | Journal of Neuroinflammation, Jg. 20 (2023), Heft 1, S. 1-19 |
Veröffentlichung: | BMC, 2023 |
Medientyp: | academicJournal |
ISSN: | 1742-2094 (print) |
DOI: | 10.1186/s12974-023-02829-3 |
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