Hoseini-Aghdam Mirhamed, Sheikh Vida, Eftekharian Mohammad Mahdi, Rezaeepoor Mahsa, Behzad Mahdi
Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Department of Internal Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Immunol Lett. 2020 Sep;225:1-8. doi: 10.1016/j.imlet.2020.06.003. Epub 2020 Jun 12.
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.
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 CD4CD25 Treg cells, CD4CD25 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.
The percentage and MFI of TIGIT on CD4CD25 T cells, CD4CD25 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.
The expression of TIGIT was enhanced in T2DM and the TIGIT axis could be considered as a new therapeutic purpose for the T2DM.
2型糖尿病(T2DM)中存在侵袭性辅助性T细胞反应和调节性T(Treg)细胞功能障碍。共抑制性T细胞免疫球蛋白和免疫受体酪氨酸抑制基序结构域(TIGIT)、神经纤毛蛋白-1(Nrp-1)以及共刺激性分子CD226在免疫反应的抑制或激活中起关键作用。在本研究中,对TIGIT、CD226、Nrp-1及其配体CD155和信号素3A(Sema-3A)在T2DM中的表达进行了研究。
收集30例T2DM患者及30例健康对照(HC)的外周血单个核细胞(PBMC)。采用流式细胞术评估CD4CD25 Treg细胞、CD4CD25反应性T细胞、总CD4 T细胞和非CD4细胞上TIGIT和Nrp-1的频率。通过实时PCR评估TIGIT、CD226、Nrp-1、CD155和Sema-3A的mRNA水平。
与HC相比,患者CD4CD25 T细胞、CD4CD25 T细胞、总CD4 T细胞和非CD4细胞上TIGIT的百分比和平均荧光强度(MFI)更高(所有p均<0.05)。与HC相比,患者TIGIT的mRNA水平升高(p = 0.003)。两组之间CD226、CD155、Nrp-1和Sema-3A的表达未观察到差异。
T2DM中TIGIT的表达增强,TIGIT轴可被视为T2DM的一个新的治疗靶点。