ISSN: 1838-7640Theranostics
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Theranostics 2020; 10(9):4250-4264. doi:10.7150/thno.43731 This issue Cite
Research Paper
Bcl-6-directed follicular helper T cells promote vascular inflammatory injury in diabetic retinopathy
1. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, P. R. China
2. Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, P.R. China.
Citation:
Liu Y, Yang Z, Lai P, Huang Z, Sun X, Zhou T, He C, Liu X. Bcl-6-directed follicular helper T cells promote vascular inflammatory injury in diabetic retinopathy. Theranostics 2020; 10(9):4250-4264. doi:10.7150/thno.43731. https://www.thno.org/v10p4250.htm
Other stylesAbstract
Diabetic retinopathy (DR) is a vision-threatening complication of diabetes mellitus characterized by chronic retinal microvascular inflammation. The involvement of CD4+ T cells in retinal vascular inflammation has been considered, but the specific subset and mechanism of T cell-mediated response during the process remains unclear. Here, we aim to investigate the potential role of follicular helper T (Tfh) cells, a newly identified subset of CD4+ T cells in retinal vascular inflammation in DR.
Methods: Patients with DR were enrolled and the PD-1+CXCR5+CD4+ Tfh cells were detected in the peripheral blood by flow cytometry. The streptozotocin (STZ)-induced DR model and oxygen-induced retinopathy (OIR) model were established, and 79-6, an inhibitor of Bcl-6, was injected intraperitoneally to suppress Tfh cells. The Tfh cells-related genes were investigated in the spleen, lymph nodes, and retina of mice by flow cytometry, immunofluorescence, and qPCR.
Results: The Tfh cells expanded in the circulation of patients with DR and also increased in circulation, lymph nodes and retinal tissues from the STZ-induced DR mice and OIR mice. Notably, inhibition of Bcl-6, a critical transcription factor for Tfh cells development, prevented upregulation of Tfh cells and its typical IL-21 cytokine, and ameliorated vascular leakage in DR mice or retinal angiogenesis in OIR mice, indicating that Bcl-6-directed Tfh cells could promote vascular inflammation and angiogenesis.
Conclusions: Our results suggested that excessive Bcl-6-directed Tfh cells represent an unrecognized feature of DR and be responsible for the retinal vascular inflammation and angiogenesis, providing opportunities for new therapeutic approaches to DR.
Keywords: follicular helper T cells, diabetic retinopathy, Bcl-6, IL-21
Citation styles
APA
Liu, Y., Yang, Z., Lai, P., Huang, Z., Sun, X., Zhou, T., He, C., Liu, X. (2020). Bcl-6-directed follicular helper T cells promote vascular inflammatory injury in diabetic retinopathy. Theranostics, 10(9), 4250-4264. https://doi.org/10.7150/thno.43731.
ACS
Liu, Y.; Yang, Z.; Lai, P.; Huang, Z.; Sun, X.; Zhou, T.; He, C.; Liu, X. Bcl-6-directed follicular helper T cells promote vascular inflammatory injury in diabetic retinopathy. Theranostics 2020, 10 (9), 4250-4264. DOI: 10.7150/thno.43731.
NLM
Liu Y, Yang Z, Lai P, Huang Z, Sun X, Zhou T, He C, Liu X. Bcl-6-directed follicular helper T cells promote vascular inflammatory injury in diabetic retinopathy. Theranostics 2020; 10(9):4250-4264. doi:10.7150/thno.43731. https://www.thno.org/v10p4250.htm
CSE
Liu Y, Yang Z, Lai P, Huang Z, Sun X, Zhou T, He C, Liu X. 2020. Bcl-6-directed follicular helper T cells promote vascular inflammatory injury in diabetic retinopathy. Theranostics. 10(9):4250-4264.
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