Zherebiatiev O. Immune-mediated mechanisms of inflammatory bowel disease and possibility of their correction.

The thesis is devoted to improving knowledge of the regularities and mechanisms of changes in the functional state of the gut-associated lymphoid tissue of rats with an experimental ileitis and colitis in the dynamics of their pathogenic grounded correction by simvastatin and recombinant antagonist of receptors of interleukin-1 (ARIL-1). We used histological, morphometric, immunofluorescence methods, real-time reverse transcription polymerase chain reaction, computer image analysis, statistical methods. We found and identified the main key links in the development and progression of IBD, disorders of the innate immune system is to change the distribution of TLR2+-, TLR4+- and NF-?B+-lymphocytes, changes of expression NOD- and RIG-like receptors, changes in mRNA expression levels of proinflammatory cytokines IL-1? and IL-17A, induction of gene expression of NLRP3 inflammasome and short-chain fatty acid receptors FFAR2, alarmin HMGB1 and c-Rel subunit of NF-?B. Disorders of the adaptive immune system, namely change of T-bet+ / GATA3+-cells and Foxp3+ / ROR?t+-cells ratio. Influence of environmental factors, as evidenced by the change of amount of AhR+- and Atg16+-lymphocytes and concentration of the Atg16 in lymphocytes. In our study, we proved that the administration of simvastatin ARIL-1 to rats with experimental pathology has positive effect on clinical and morphological signs of ileitis and colitis, and also influence on innate and adaptive immunity, changes in signaling via the AhR receptors and concentration of the Atg16 in cells.