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    Kamyshnyi A. M.


    About the author: Kamyshnyi A. M.
    Type of article Scentific article
    Annotation Type 1 diabetes (T1D) is a chronic disease resulting from the selective autoimmune destruction of pancreatic islet β cells. The absence and/or breakdown of immune self-tolerance to islet β cells is now recognized as the essential cause for the development of the diabetogenic autoimmune response. The thymus is the primary lymphoid organ involved in thymocyte development and thus plays a central role in establishing immune tolerance. An essential molecule in the induction of central tolerance is Autoimmune Regulator (AIRE). There is strong experimental evidence that AIRE deficiency directly results in the defective negative selection of thymocytes. AIRE is predominantly expressed in MHC class II-High, CD80-High mTECs. mTECs are unique because they can express thousands of tissue-specific self-antigens that are presented to developing thymocytes and are thus associated with negative selection. In addition to mTECs, some recent studies have also identified the AIRE protein in thymus and peripheral lymph nodes lymphocytes both in humans as well as mice. The aim of research. The aim of this study was to investigate of AIRE protein expression in rat thymus with experimental diabetes mellitus were investigated and discussed in experimental work. Materials and methods. Investigations were carried out on 28 male rats Vistar line 5-6 months of age. EDM was designed by intraperitoneal injection of streptozotocyn (SIGMA, USA) at dose 50 mg/kg one time. Method of double immunofluorescence with usage of rat monoclonal anti-AIRE, anti-СD4 and rat anticytokeratin antibodies was used for revelation of AIRE. Structure of a thymus was analyzed with the help of software VIDAS. All statistical analyses were performed using EXCEL MS Office 2010 (Microsoft Corp., USA), STATISTICA 6.0 (Stat-Soft, 2001) software. Results are expressed as mean values ± SEM. Differences were considered statistically significant if the p value was <0.05. Results. It has been established that quantity of control animals’ thymus cortical zone AIRE+-cells was in 2 times lower than in medullar zone. In this connection thymus epithelioreticulocytes (AIRE+MAPC+) were identified at the same time with a large quantity of thymocytes (AIRE+CD4+). Development of EDM has not accompanied by any changes in quantity of AIRE+-cells in thymus cortical zone, whereas their quantity has been decreased by 35% comparably with control animal group. It has been noticed that concentration of AIRE protein in diabetic rats were reliably decreased comparably with control in AIRE+-cells of both investigated thymus zones. Conclusions. In summary, although the effects of AIRE on central tolerance are well established, the cellular and molecular mechanisms are still unclear. Along with the better-understood effects on TSA expression, AIRE can also alter the differentiation program of mTECs, regulate the expression of thymic chemokines, contribute to specific Treg induction, and induce mTEC apoptosis. This novel knowledge of normal and pathologic functions of the thymus constitutes a solid basis for the development of a novel type of tolerogenic/negative self-vaccination against type 1 diabetes (T1D).
    Tags AIRE, thymus, diabetes mellitus
    • Anderson M. Projection of an immunological self shadow within the thymus by the Aire protein / M. Anderson, E. Venanzi, L. Klein // Science.-2002.- Vol.298.-P. 1395-1401.
    • Anderson G. Generating intrathymic microenvironments to establish T-cell tolerance / G. Anderson, P. Lane, E. Jenkinson // Nature Rev. Immunol.-2007.-Vol. 7.-P. 954–963.
    • Chentoufi A. Advances in type I diabetes associated tolerance mechanisms / A. Chentoufi, N. Binder, N. Berka // Scand. J. of Immunol.-2008.-Vol. 68.-P. 1–11.
    • Derbinski J. Promiscuous gene expression in thymic epithelial cells is regulated at multiple levels/ J. Derbinski, J. Gabler, B. Brors // J. Exp. Med.- 2005.-Vol. 202.-P. 33-45.
    • Holmdahl R. Aire-ing self antigen variability and tolerance // Eur. J. Immunol.-2007.-Vol. 37.-P. 598–601.
    • Hässler S. Аire deficiency causes increased susceptibility to streptozotocin-induced murine type 1 diabetes/ S. Hässler, L. Peltonen, S. Sandler // Scand. J. Immunol.- 2008.-Vol. 67.-P. 569-580.
    • Kont V. Modulation of Aire regulates the expression of tissue-restricted antigens/ V.Kont, M.Laan, K.Kisand // Mol. Immunol.- 2008.-Vol. 45.-P. 25–33
    • Li J. Developmental pathway of CD4+CD8- medullary thymocytes during mouse ontogeny and its defect in Aire–/–mice/ J. Li, Y. Li, J. Yao // Proc. Natl. Acad. Sci. USA.- 2007.-Vol. 104.-P. 18175–18180.
    • Mathis D. A decade of AIRE / D. Mathis, C. Benoist // Nature Reviews Immunology.- 2007.-Vol. 7.-P. 645-650.
    • Nagafuchi S. Аutoimmune regulator (AIRE) gene is expressed in human activated CD4+ T-cells and regulated by mitogen-activated protein kinase pathwaу/ S. Nagafuchi, H. Katsuta, R. Koyanagi // Microbiol. Immunol.- 2006.-Vol. 50.-P. 979-987.
    • Suzuki E. Expression of AIRE in thymocytes and peripheral lymphocytes / E. Suzuki, Y. Kobayashi, O. Kawano // Autoimmunity.-2008.-Vol 41.-P. 133-139.
    Publication of the article «World of Medicine and Biology» №2(50) 2 part 2015 year, 120-123 pages, index UDK 612.438.017.1:616.379-008.64-092.9