THE EXPERIMENTAL MODEL OF AUTOIMMUNE PROCESS: THE ROLE OF EPIGENETIC VARIATION IN THE POPULATION OF MICE HYBRIDS

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Abstract

Background: At the development of graft versus host disease in genetically homogeneous population of (C57Bl/6 x DBA/2) F1 mice two clinical phenotypes of SLE-like disease were revealed: lupus+ (immune complex glomerulonephritis and hemolytic anemia) and lupus – (hemolytic anemia). The GvHD phenotypic heterogeneity is determined by the Th1 /Th2-polarization: Th2 lymphocyte predominant activity, leads to the lupus+ development, or prevalence activity of Th1 cells, leads to the lupus– development. Objective: Our aim was to evaluate the possibility of using an experimental model of autoimmune disease for studying and testing of epigenetic modifications, shifting Th1 /Th2-
balance in vivo. Methods: Сhronic GVHD was induced in B6D2F1 mice by the transplantation of 130×10 6 parental DBA/2 splenocytes. Аnti-ds-DNA, total IgG and IgG1, IgG2а Abs were measured by ELISA. Results: Six- to 8-week-old female DBA/2 and B6D2F1 mice were obtained from Biological Research Laboratory (Novosibirsk). It was established that regular moderate physical activity (unladed swimming) shifted Th1 /Th2 balance towards Th1. This leads to a decrease in a population of recipients the lupus+ mice from 57 to 26% (p <0,001) with significantly reduced hypergammaglobulinemia (IgG from 2,8 to 2,0 mg/ml; p <0,047) and DNA antibodies titer from 0,18 to 0,12 OD (p =0,05). Administration of epigenetic modificator bisphenol A at low doses, which mimicking estrogen effects, enhances the proportion of lupus+ mice in experimental groups from 33 to 64% (p <0,001) and impairs their clinical status by the increasing the urine protein level from 2.8 to 4,2 mg/ml (p <0,001) in animals. Conclusion: Th1 /Th2 – balance presumably is determined by the immune system epigenetic modification in experimental mice, formed on the previous stages of ontogeny and defines the direction of immune processes development in individual animal.


About the authors

O. P. Kolesnikova

Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation

Author for correspondence.
Email: iscreen2001@mail.ru

доктор медицинских наук, руководитель лаборатории экспериментальной иммуноте-
рапии НИИ фундаментальной и клинической иммунологии
Адрес: 630099, Новосибирск, ул. Ядринцевская, д. 14, тел.: +7 (383) 222-06-72

Russian Federation

O. T. Kudaeva

Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation

Email: iscreen2001@mail.ru

доктор биологических наук, ведущий научный сотрудник лаборатории эксперимен-
тальной иммунотерапии НИИ фундаментальной и клинической иммунологии

Russian Federation

N. N. Vol'skii

Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation

Email: dtheory@yandex.ru

кандидат медицинских наук, ведущий научный сотрудник лаборатории эксперимен-
тальной иммунотерапии НИИ фундаментальной и клинической иммунологии
Адрес: 630099, Новосибирск, ул. Ядринцевская, д. 14, тел.: +7 (383) 222-06-72

Russian Federation

E. V. Goiman

Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation

Email: l.goiman@mail.ru

кандидат медицинских наук, научный сотрудник лаборатории экспериментальной
иммунотерапии НИИ фундаментальной и клинической иммунологии
Адрес: 630099, Новосибирск, ул. Ядринцевская, д. 14, тел.: +7 (383) 222-06-72

Russian Federation

E. D. Gavrilova

Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation

Email: edav.gavr@mail.ru

кандидат биологических наук, старший научный сотрудник лаборатории эксперимен-
тальной иммунотерапии НИИ фундаментальной и клинической иммунологии
Адрес: 630099, Новосибирск, ул. Ядринцевская, д. 14, тел.: +7 (383) 222-06-72

Russian Federation

O. M. Perminova

Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation

Email: pom.57@yandex.com

кандидат медицинских наук, научный сотрудник лаборатории экспериментальной
иммунотерапии НИИ фундаментальной и клинической иммунологии
Адрес: 630099, Новосибирск, ул. Ядринцевская, д. 14, тел.: +7 (383) 222-06-72

Russian Federation

E. N. Demchenko

Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation

Email: elena.demchenko@gmail.ru

кандидат химических наук, научный сотрудник лаборатории экспериментальной
иммунотерапии НИИ фундаментальной и клинической иммунологии
Адрес: 630099, Новосибирск, ул. Ядринцевская, д. 14, тел.: +7 (383) 222-06-72

Russian Federation

V. A. Kozlov

Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation

Email: vakoz40@yandex.ru

доктор медицинских наук, профессор, академик РАН, директор НИИ фундамен-
тальной и клинической иммунологии
Адрес: 630099, Новосибирск, ул. Ядринцевская, д. 14, тел.: +7 (383) 222-26-74

Russian Federation

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