Subconjunctival injection of human umbilical cord mesenchymal stem cells alleviates experimental allergic conjunctivitis via regulating T cell response

Stem Cell Research & Therapy

Research

Caixia Jin¹  Michael Mingze Lu¹  Juan Wang¹  Qi Shen¹  Dongli Li¹  Qingjian Ou¹  Furong Gao¹  Jiao Li¹  Jing-Ying Xu¹  Lixia Lu¹  Jieping Zhang²  Haibin Tian²  Guo-Tong Xu³  Jingfa Zhang⁴ 

[1] Department of Ophthalmology of Tongji Hospital, Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, 389 Xincun Road, 200065, Shanghai, China;Department of Ophthalmology of Tongji Hospital, Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, 389 Xincun Road, 200065, Shanghai, China;Department of Physiology and Pharmacology, TUSM, 200092, Shanghai, China;Department of Ophthalmology of Tongji Hospital, Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, 389 Xincun Road, 200065, Shanghai, China;Department of Physiology and Pharmacology, TUSM, 200092, Shanghai, China;The Collaborative Innovation Center for Brain Science, Tongji University, 200092, Shanghai, China;Department of Ophthalmology, Shanghai General Hospital (Shanghai First People’s Hospital), Shanghai Jiao Tong University, 200080, Shanghai, China;

关键词: Allergic conjunctivitis;    Human umbilical mesenchymal stem cells;    Immunomodulatory;    Subconjunctival injection;    Th2 cells;   

DOI  :  10.1186/s13287-023-03484-4

 received in 2023-06-19, accepted in 2023-08-29,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundT helper 2 (Th2) cells are thought to play critical roles in allergic conjunctivitis (AC). They release inflammatory cytokines to promote an allergic response in AC. Due to individual heterogeneity and long-term chronic management, current therapies do not always effectively control AC. Mesenchymal stem cells (MSCs) have been shown to be effective in treating allergy-related disorders, but it is unclear how exactly the Th2-mediated allergic response is attenuated. This study aims to elucidate the therapeutic effect and mechanism of the human umbilical cord MSCs (hUCMSCs) in a mouse model of experimental AC (EAC).MethodsA mouse EAC model was established by inoculating short ragweed (SRW) pollen. After the SRW pollen challenge, the mice received a single subconjunctival or tail vein injection of 2 × 106 hUCMSCs, or subconjunctival injection of hUCMSCs conditioned medium (hUCMSC-CM), and dexamethasone eye drops was used as positive control; subsequent scratching behavior and clinical symptoms were assessed. Immunostaining and flow cytometry were carried out to show allergic reactions and the activation of CD4 + T cell subsets in the conjunctiva and cervical lymph nodes (CLNs). Gene expression was determined by RNA-seq and further verified by qRT-PCR and Western blot. Co-culture assays were performed to explore the regulatory role of hUCMSCs in the differentiation of CD4 + naive T cells (Th0) into Th2 cells.ResultsSubconjunctival administration of hUCMSCs resulted in fewer instances of scratching and lower inflammation scores in EAC mice compared to the tail vein delivery, hUCMSC-CM and control groups. Subconjunctival administration of hUCMSCs reduced the number of activated mast cells and infiltrated eosinophils in the conjunctiva, as well as decreased the number of Th2 cells in CLNs. After pretreatment with EAC mouse serum in vitro to mimic the in vivo milieu, hUCMSCs were able to inhibit the differentiation of Th0 into Th2 cells. Further evidence demonstrated that repression of Th2 cell differentiation by hUCMSCs is mediated by CRISPLD2 through downregulation of STAT6 phosphorylation. Additionally, hUMCSCs were able to promote the differentiation of Th0 cells into regulatory T cells in CLNs of EAC mice.ConclusionsSubconjunctival injection of hUCMSCs suppressed the Th2-allergic response and alleviated clinical symptoms. This study provides not only a potential therapeutic target for the treatment of AC but also other T cell-mediated diseases.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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