Study of the Role of Fas-Mediated Apoptosis of Peripheral Blood T-Lymphocytes in the Pathogenesis of Type 1 Diabetes Mellitus
Lugovaya AV1*, Mitreikin VPH2, Kalinina NM3
1Pavlov State Medical University, Saint Petersburg, Russian Federation
2Professor, Department of Pathological Physiology, Pavlov State Medical University, Saint Petersburg, Russian Federation
3Professor, Department of Immunology, Pavlov First Saint Petersburg State Medical University, Leading Research Associate, Nikiforov Russian Center of Emergency and Radiation Medicine, Saint Petersburg, Russian Federation
*Corresponding Author: Lugovaya AV, Pavlov State Medical University, Saint Petersburg, Russian Federation.
April 29, 2022; Published: May 30, 2022
Introduction: It is known that impaired activation of Fas-mediated apoptosis in certain subpopulations of T cells plays an important role in the pathogenesis of type 1 diabetes mellitus (T1DM). The key point in the initiation of CD-1 is the resistance to apoptosis of activated autoreactive T-lymphocytes, which migrate from the bloodstream to the pancreas and are actively involved in the destruction of b-cells. It has been established that the Fas/FasL system plays a central role in maintaining peripheral autotolerance and tissue homeostasis of the body. Fas-mediated apoptosis is induced by binding of the Fas (CD95/APO-l/TNFRSF6)-receptor to the Fas(CD95L/CD178/TNFSF6)-ligand on the respective cells. Triggering the expression of cell surface Fas receptors (Fas) regulates the elimination of autoreactive T and B lymphocytes by apoptosis. To date, most of the results on the study of Fas-mediated apoptosis in T1DM have been obtained in experiments in vitro. There is no doubt that autoimmune changes in vivo are more profound, and the extrapolation of effects detected in the in vitro system to the body is not always valid.
The Aim: of the study was to evaluate the effectiveness of Fas-mediated apoptosis of T-lymphocytes in the blood of patients with T1DM depending on the phase of compensation and the duration of the course of the disease, as well as in individuals with a high risk of developing T1DM.
Material and Methods: We examined 63 patients with a reliably established diagnosis of T1DM and 15 people with a high risk of developing T1DM. The control group consisted of 30 healthy individuals, comparable in sex and age to patients with T1DM. Biomarkers of Fas-mediated apoptosis of peripheral blood lymphocytes in patients with T1DM and those at high risk of developing T1DM were studied. The surface expression of the Fas receptor in individual subpopulations of T-lymphocytes was assessed by flow cytometry. The concentration of soluble forms of the Fas receptor (sFas) and Fas ligand (sFasL) in the blood serum of the examined patients was studied by indirect enzyme-linked immunosorbent assay (ELISA).
Results: It has been established that in patients in the decompensation phase of T1DM, inhibition of Fas-mediated apoptosis of autoreactive CD95+ cells occurs with the participation of the soluble form of the Fas receptor (sFas-soluble Fas). When carbohydrate metabolism is compensated, apoptosis of lymphocytes is observed along the Fas pathway with the help of a soluble form of the Fas ligand (sFasL-soluble FasL). In the compensation phase of T1DM and in individuals at risk, an increase in the content of sFasL was revealed. This probably has a protective value, since, according to the literature, sFasL is involved in the removal of autoreactive CD95+ cells in the peripheral blood.
Conclusions: The results obtained indicate a pronounced dysregulation in the Fas/FasL system, which is observed at all stages of the development of T1DM. The study found that the regulation of the FasL/Fas system affects the tropism of autoreactive T cells to islet antigens in patients with T1DM, and that Fas-induced death of β-cells mediated by T lymphocytes plays a significant role in the development and progression of T1DM, both in the latent stage and at the stage of advanced clinical manifestations of the disease.
Key words: Apoptosis; Type 1 Diabetes Mellitus; Death Receptors; Fas-Mediated Apoptosis; Fas Receptor; Fas Ligand; T Lymphocytes; Β -Cells of the Pancreas.
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