Journal Article

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

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

2023

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Advertising executives / Analysis / Animal models / Animals / Antibodies / Antigens / Autoimmune Diseases / Autoimmune uveitis / Biomedical and Life Sciences / Biomedicine / Blindness / Brain research / Care and treatment / Cell activation / Cell differentiation / Cell migration / Cells / CXCR4 protein / Development and progression / Diagnosis / Disease / Disease Models, Animal / Dosage and administration / Experimental autoimmune uveitis / Experimental autoimmune uveoretinitis / Eye diseases / Female / Females / Flow cytometry / Genetic aspects / Granulocyte-macrophage colony-stimulating factor / Health aspects / Helper cells / Homeostasis / Hormones / Id2 / Immune response / Immune system / Immunology / Immunomodulation / Inflammation / Interleukin 23 / Lymphocytes T / Mice / Mice, Inbred C57BL / Morbidity / Neurobiology / Neurology / Neurosciences / Pathogenicity / Polyethylene glycol / Pregnancy / Pregnant women / Prevention / Progesterone / Progesterone - pharmacology / Progesterone - therapeutic use / Remission / Risk factors / RNA / RNA sequencing / Single-cell RNA sequencing / Th17 Cells / Transcription factors / Treg / Uveitis / Virulence