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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