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THE EXPERIMENTAL MODEL OF AUTOIMMUNE PROCESS: THE ROLE OF EPIGENETIC VARIATION IN THE POPULATION OF MICE HYBRIDS
- Authors: Kolesnikova O.P.1, Kudaeva O.T.1, Vol'skii N.N.1, Goiman E.V.1, Gavrilova E.D.1, Perminova O.M.1, Demchenko E.N.1, Kozlov V.A.1
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Affiliations:
- Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation
- Issue: Vol 70, No 2 (2015)
- Pages: 152-158
- Section: PROCEEDINGS of the GENERAL MEETING of the Department of Medical Sciences, RAS
- URL: https://vestnikramn.spr-journal.ru/jour/article/view/50
- DOI: https://doi.org/10.15690/vramn.v70i2.1307
- ID: 50
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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
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
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
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
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
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
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
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
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