revealed an allele-specific preference in protein binding at this site of CD-specific open chromatin. CONCLUSIONS: We demonstrate that different genomic loci exhibit distinct chromatin changes that play active roles in shaping the response in LP macrophages to the enteric microbiota. These chromatin features are dynamic and regulated by IL-10 and the enteric microbiota. These findings introduce the possibility of modulating chromatin regulators with small molecules for the treatment of CD.BACKGROUND: The FVB.mdr1a2/2 mouse, lacking the small molecule pump Pglycoprotein (P-gp), is a commonly used model for the study of spontaneous T cell mediated colitis. In addition, MDR1 polymorphisms and decreased P-gp function in humans has been linked to the development of ulcerative colitis. Since P-gp is expressed on the apical epithelium of organs and due to the role of P-gp in toxin extrusion, we have hypothesized that P-gp's physiological function is to extrude xenobiotic substrates from the internal environment. The absence of P-gp results in an alteration of the epithelial barrier, increasing permeability to ions, bacterial toxins, and other molecules that could potentially include environmental aryl hydrocarbon receptor (AhR) ligands. This study aims to determine the mechanism by which intestinal inflammation develops in FVB.mdr1a2/2 mice. METHODS: We have utilized the FVB.mdr1a2/2 mouse to investigate the development of individual T-cell subsets in the presence or absence of the AhR ligand 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD). T-helper cell development has been evaluated by flow cytometry, RT-PCR, explants, and ELISAs. RESULTS: Recently, our lab has shown that FVB.mdr1a2/2 mice, prior to the development of histological inflammation, have a significant decrease in Foxp3+ regulatory T cells (Tregs) in Peyer's patches (PP) and intestinal lamina propria, but not in spleen and mesenteric lymph nodes (MLN). This decrease in Tregs appears to be due to an inappropriate response to the regulatory cytokine, transforming growth factor beta (TGFb), a cytokine known to be responsible for induced Treg (iTreg) generation. Naïve T-cells from the FVB.mdr1a-/-mouse, when exposed to TGFb, produce IL17 instead of increasing their expression of FoxP3. To further investigate this response and to determine if P-gp alters the impact of AhR ligands on immune responses we treated explants and CD4+ T-cells from FVB and FVB.mdr1a2/2 mice with TCDD. As has been previously reported, the control FVB mice reduced the projection of the TH17 cytokines IL17 and IL22 when exposed to TCDD. However, in the absence of Pgp, TCDD treatment had the opposite effect. There was a dramatic increase in both IL22 and IL17. CONCLUSIONS: This opposite effect of TCDD on cytokine production is the absence of P-gp is consistent with our hypothesis that the P-gp pump is necessary in normal intestinal homeostasis to extrude AhR ligands, such as TCDD.

In the article, the authors pay attention to the place and significance of animals in the system of civil rights objects. The article provides a General analysis of legal acts that fix the specifics of the legal regime of animals. The article analyzes the specifics of the legal regime of animals. Special attention is paid to the analysis of the place of animals in the system of civil rights objects. The authors raise the issue of the absence of a unified concept of an animal in the current legislation, and also draw attention to the lack of a unified approach to the classification of animals, which may be of practical importance when applying legal standards in the field under consideration. The authors analyze the features of legal regulation of the involvement of wild animals and animals removed from their natural habitat. The authors conclude that there is currently a fairly logical and consistent legal framework in place for wild animals, but due attention is notpaid to the specifics of the legal regime for animals removed from their natural habitat. The article attempts to determine the types of animals whose legal regime features are provided for in the current legislation. The article indicates that new regulatory legal acts are currently being adopted on the treatment of animals, in particular, the concept of potentially dangerous dogs has been introduced into legal circulation.