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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2019; 65(6): 61-69


STUDING OF DISTRIBUTION OF FOXP3+ AND RORγt+ LYMPHOCYTES IN GUT-ASSOSIATED LIMPHOID TISSUE OF RATS AT AN EXPERIMENTAL DIABETES MELLITUS AND ADMINISTRATION OF INDERECT INHIBITORS OF TUMOR NECROSIS FACTOR α

A.S. Degen, A.M. Kamyshny

    Zaporizhzhya State Medical University, Ukraine
DOI: https://doi.org/10.15407/fz65.06.061

Abstract

A lot of researches concerning T1DM and its animal models have shown a close connection of autoimmune diabetes development and changes in the intestinal tract, which anticipate appearance of clinical symptoms of the disease. Functional polarization of T-helpers in gut-associated lymphoid tissue plays an important role in an induction of development and progression of T1DM. Of great interest is studying of adaptive immune system, especially a tight regulation of Treg/Th17 ratio, role in diabetes progression. The balance between Treg and Th17 controls inflammation and is responsible for the proper functioning of the immune system. A decrease of Tregs and/or increase of Th17 may induce local inflammation, which in turn may hasten the development of diabetic complications. Proinflammatory cytokines, such as TNFα, play one of the most important roles in pathogenesis of T1DM. Indirect inhibitors of their production (for example, pentoxifylline) reduce risk of development of this pathology. The aim of our work was to study the peculiarities of FOXP3 and RORγt transcription factors in gut-associated lymphoid tissues (GULT) in rats with experimental streptozotocin-induced diabetes mellitus and under pentoxifilline administration. The researchers were made on Wistar rats. For an induction of diabetes streptozotocin was used in a dose of 50 mg/kg. Structure of population of FOXP3+ and RORγt+-cells has been studied by the analysis of serial histological sections using the method of indirect immunofluorescense with monoclonal antibodies to FOXP3 and RORγt of rat. It has been established that diabetes development was accompanied with 46–75 % increase in quantity of RORγt+- cells and with 22-46% decrease in quantity of FOXP3+-cells, and also leads mainly to growth of RORγt concentration and decrease of FOXP3 concentration in immunopositive cells. Pentoxifilline administration of diabetic animal reduces the quantity of RORγt+-cells in mucous membrane of villus by 18–32 % and in subepithelial zone of isolated lymphoid follicle’s (ILF) in 1.5–2.0 times. Quantity of Treg in both regions increased on 47–74 % by 4th week of the pathology development only. Thus, concentration of FOXP3 increased on 2nd week of diabetes development, and concentration of RORγt mainly showed dynamics to decrease. Treg/Th17 ratio at the experimental T1DM showed dynamics to decrease in both morpho-functional regions throughout the research period (in mucous membrane of villus by 21–43 % and in ILF by 68 %,). Pentoxifilline administration led to change of the ratio in an increase direction in mucous membrane of villus 2.4 times (P<0,05) on 4th week and in ILF 1.5–2.1 times (P< 0,05) throughout the research period. The expression augmentation with FOXP3 and RORγt in ileum immunopositive cells can influence the differentiation of subsets of T-helpers and their proinflammatory cytokines production, thus acting as one of triggers of diabetes development and progression.

Keywords: diabetes; FOXP3; RORγt; gut-associated lymphoid tissue.

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