Dysregulation of circulating CD4 + CXCR5 + PD-1+ T cells in diabetic retinopathy

Diabetic retinopathy (DR) is one of the most serious complications of diabetes and a leading cause of vision loss and blindness worldwide.1 Inflammatory cells have an important role in the early lesions of DR. These include exudation caused by the destruction of the blood-retinal barrier, and in the pathogenesis of advanced proliferative DR (PDR), leading to neovascularization, vitreous hemorrhage, and traction retinal detachment.2

Chronic low-grade inflammation has been identified as an immunopathological change in DR.2 This is associated with a variety of events, including the upregulation of inflammatory mediators and activation and transport of immune cells, particularly CD4 + T cells, which are recruited with other immune cells, thus leading to inflammation and accelerated vascular damage.2., 3.

Follicular helper T (Tfh) cells are a relatively new subgroup of CD4+ T cells located at the germinal center (GC). This subgroup has attracted close attention because of its important role in the following: immune responses to vaccines, autoimmune diseases, allergies, organ transplantation, protective immunity with malignant tumors, and other biological processes.4 Tfh cells are classically present in secondary lymphoid organs, with a few similar cells in the blood called circulating Tfh cells.5 Tfh cells, most commonly CXCR5 + CD4 + PD-1+ cells, are involved in helping B cells undergo proliferation, homotypic transformation, and somatic cell mutation, thus producing a lasting antibody response. In addition to their limited role in GCs, circulating Tfh cells residing in the extrafollicular region may contribute to disease independent of helping the antibody response.3., 6.

Studies have revealed that CD4 + CXCR5+ T cells in peripheral blood have the same functional characteristics as Tfh cells of secondary lymphoid organs and could help B cells via IL-21 production.7

B-cell lymphoma-6 (Bcl-6) is an important transcription factor for Tfh cell differentiation. Bcl-6 regulates the production and differentiation of Tfh cells through various mechanisms.8

C-X-C motif ligand 13 (CXCL13), also known as B-lymphocyte chemokine-1, is an important chemokine. It directs migration before B cells differentiate into antibody-secreting cells. Tfh cells are the main source of CXCL13, and serum CXCL13 levels suggest that Tfh cells play a role in B-cell-mediated humoral immunity.4., 9.

The changes regarding Tfh cells and serum Bcl-6 and CXCL13 levels in type 2 diabetes patients with DR during different stages and the relationship with clinical parameters require further exploration. Therefore, we aimed to determine the proportion of CD4 + CXCR5 + PD-1 + Tfh cells in the peripheral blood and levels of Bcl-6 and CXCL13 in serum and analyze the relationship between Tfh cells, Bcl-6 and CXCL13 in type 2 diabetic patients with different stages of DR. This study investigated the association between Tfh cells and the levels of Bcl-6 and CXCL13, as well as the role of circulating Tfh cells and serum levels of Bcl-6 and CXCL13 in the pathogenesis of DR.

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