No abstract

During the process of acute colitis, the subsequent inflammatory environment presumably results in changes of fcDNA with the potential to facilitate the downregulation of inflammation and improvement of regeneration. Thus, preconditioning of mice with colitis-derived fcDNA via TLR9 signaling could exert a tissue-protective effect and influence beneficially the course of DSS-colitis. Elucidating mechanisms of immune response alterations by nucleic acids may provide further insight into the etiology of IBD and develop the basis of novel immunotherapies.

In inflammatory bowel diseases the presence of free-circulating DNA (fcDNA) sequences in the sera is an established phenomenon, albeit its real biological function still remains unclear. In our study the immunobiologic effects of a single-dose, intravenously administered fcDNA of normal and colitic origin were assayed in DSS-colitic and control mice. In parallel with disease and histological activity evaluations changes of the TLR9 and inflammatory cytokine signaling gene expression profiles were assayed in isolated cells of the lamina propria. Intravenously administered colitis-derived fcDNA displayed a more prominent beneficial action regarding the clinical and histological severity of DSS-colitis than that of fcDNA of normal origin. Systemic administration of colitis-derived fcDNA significantly altered the expression of certain TLR9-related and proinflammatory cytokine genes in a clinically favorable manner. Presumably due to induction of severe colitis, the subsequent marked inflammatory environment may result changes in fcDNA with a potential to promote the downregulation of inflammation and improvement of tissue regeneration. Elucidating mechanisms of innate immune alterations by nucleic acids may provide further insight into the etiology of inflammatory bowel diseases, and develop the basis of novel nucleic acid-based immunotherapies.

No abstract

Gut-associated lymphoid tissue (GALT) is supposed to play an integral role in the organization of colonic repair mechanisms. Majority of the GALT is composed of isolated and aggregated lymphoid follicles distributed throughout the intestines. These lymphoid follicles, including Peyer's patches of the small, and isolated lymphoid follicles (ILFs) of both the small and large intestines, are composed of a specialised follicle associated epithelium overlying a subepithelial dome containing numerous dendritic cells, macrophages, T and B cells. Within inflammatory conditions the number, the diameter and the density of ILFs are increasing. Follicles are involved not just in immune surveillance, but their presence is also indispensable for normal colonic mucosal regeneration. Regarding mucosal repair the relation of ILFs to bone marrow derived stem cells, follicular dendritic cells, subepithelial myofibroblasts and crypt formations, and the putative organizer role of ILFs have not been clarified yet.