Bcl-6-directed follicular helper T cells promote vascular inflammatory injury in diabetic retinopathy.

Abstract

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.

• Authors: Yan Liu, Ziqi Yang, Peilong Lai, Zijing Huang, Xiaowei Sun, Tian Zhou, Chang He, Xialin Liu
• Journal: Theranostics (Theranostics) Vol. 10 Issue 9 Pg. 4250-4264 ( 2020) ISSN: 1838-7640 [Electronic] Australia
• PMID: 32226551 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The author(s).

Chemical References

• BCL6 protein, human
• Interleukins
• Proto-Oncogene Proteins c-bcl-6
• interleukin-21

Topics

• Animals
• Diabetic Retinopathy (immunology)
• Female
• Humans
• Inflammation (immunology)
• Interleukins (immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Middle Aged
• Proto-Oncogene Proteins c-bcl-6 (immunology)
• Retina (immunology, pathology)
• T Follicular Helper Cells (cytology)