Enhanced expression of TIGIT but not neuropilin-1 in patients with type 2 diabetes mellitus

Abstract

Background: The aggressive T helper cell responses and regulatory T (Treg) cells dysfunction exist in type 2 diabetes mellitus (T2DM). The co-inhibitory T cell immunoglobulin and ITIM-domain (TIGIT), neuropilin-1 (Nrp-1), and the co-stimulatory CD226 play a critical role in the inhibition or activation of immune responses. In this project, the expression of TIGIT, CD226, Nrp-1, and their ligands, CD155 and semaphorin 3A (Sema-3A) were investigated in T2DM.

Methods: Peripheral blood mononuclear cells (PBMCs) were collected from 30 patients with T2DM, and 30 healthy controls (HCs). The frequencies of TIGIT and Nrp-1 on CD4⁺CD25^hi Treg cells, CD4⁺CD25^- responder T cells, total CD4⁺ T cells, and non-CD4⁺ cells were assessed using flow cytometry. The mRNA levels of TIGIT, CD226, Nrp-1, CD155, and Sema-3A were assessed by real-time PCR.

Results: The percentage and MFI of TIGIT on CD4⁺CD25^hi T cells, CD4⁺CD25^- T cells, total CD4⁺ T cells, and non-CD4⁺ cells were higher in patients versus HCs (p < 0.05 for all). The mRNA level of TIGIT was increased in patients compared with HCs (p = 0.003). No differences were observed in the expression of CD226, CD155, Nrp-1, and Sema-3A between the groups.

Conclusions: The expression of TIGIT was enhanced in T2DM and the TIGIT axis could be considered as a new therapeutic purpose for the T2DM.

Keywords: Neuropilin-1; Regulatory T cell; TIGIT; Type 2 Diabetes mellitus.