Search

Proton pump inhibitors (PPIs), such as omeprazole, are the most commonly prescribed drugs. Treatment with PPIs alters gut microbiota composition and reduces the production of reactive oxygen (ROS) and proinflammatory IL-1β, IL-6, and TNF-α cytokines. Here, using the T cell-dependent contact hypersensitivity (CHS) response, an animal model of allergic contact dermatitis (ACD) that affects up to 30% of the population, we demonstrated that a two-week omeprazole treatment suppresses the development of CHS. Omeprazole treatment before CHS induction, reduced inflammatory response in ears measured by ear swelling, ear biopsy weight, MPO activity, and proinflammatory cytokine production. These changes were associated with reduced frequency of TCRαβ+ CD4+ IL-17A+ and TCRαβ+ CD8+ IL-17A+ T cells and increased frequency of TCRαβ+ CD4+ CD25+ FoxP3+ Treg, and TCRαβ+ CD4+ IL-10+ Tr1 cells in peripheral lymphoid organs. Omeprazole treatment decreased the production of ROS, TNF-α, and IL-6, which supported Th17 cell induction, and increased the frequency of Clostridium cluster XIVab and Lactobacillus, implicated in Treg cell induction. The fecal microbiota transplantation (FMT) experiment confirmed the role of omeprazole-induced changes in gut microbiota profile in CHS suppression. Our data suggests that omeprazole ameliorates inflammatory response mediated by T-cells.

Introduction It is well known that the microbiota of the human body is important for human health. The latest technological advances in molecular biology not only confirm the presence of microbial communities in the digestive, respiratory and urinary tracts, but have also led to the detection of the presence of microbiota in niches, previously considered as sterile, for example, in the uterus. Objective In this review we attempt to define the composition of uterine microbiota and its physiological role in the female genital tract. Moreover, we present possible consequences of changes in uterine microbiota composition on the development of gynaecologic disorders. State of knowledge Recent findings suggest the presence of bacteria in amniotic fluid, the umbilical cord blood and in the placenta. This data imply the influence of the uterine microbiota on reproductive and obstetric outcomes, as well as on foetal development and health status. The state of uterine microbiota can influence the efficiency of assisted reproductive technology. Some evidence suggesting a relationship between prenatal microbiota exposure and increased predisposition to some diseases in adulthood is particularly important. Conclusions The influence of the uterine microbiota on fertility disorders, foetus development and newborn health is an important direction of research. In the future, the status of uterine microbiota should play an important role in everyday clinical practice.

Insulin is a key autoantigen in Type 1 Diabetes (T1D), targeted by both T and B cells. Therefore, understanding insulin-specific T:B cell interactions is important. We have previously reported an insulin-reactive CD4+ T cell, (designated 2H6). Unlike other insulin-reactive T cells, 2H6 cells protect non-obese diabetic (NOD) mice from T1D development, mediated by TGFβ. To investigate insulin-specific T:B cell interactions, we bred 2H6αβ T cell receptor transgenic NOD mice (2H6) with the insulin-reactive B cell receptor transgenic NOD mice (VH125), generating 2H6VH125 NOD mice. Similar to 2H6 mice, 2H6VH125 mice are protected from T1D development. Interestingly, VH125 B cells did not alter the phenotype of 2H6 T cells; however, 2H6 T cells significantly altered the VH125 B cells by reducing the insulin-reactive non-germinal center (GC) and GC B cells, as well as MHC and costimulatory molecule expression on the B cells. Furthermore, the B cells in 2H6VH125 NOD mice exhibited increased non-insulin-specific and a class switched IgG isotype, which can be recapitulated in vivo in Rag-deficient NOD mice by adoptive transfer. In vitro, VH125 B cells from 2H6VH125 mice suppressed the proliferation of 2H6 T cells to insulin antigen but enhanced TGFβ secretion by 2H6 T cells from 2H6VH125 mice compared to 2H6 mice. In summary, our data showed that 2H6 CD4+ T cells alter the phenotype and function of insulin-reactive B cells from pathogenic to tolerogenic cells. In turn, VH125 B cells also modulate the function of the 2H6 T cells. Thus, promoting the interactions between antigen-specific regulatory T cells and B cells may lead to protection from T1D.