Estriol and commensal microflora strains regulate innate lymphoid cells functional activity in multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease in which the immune system attacks myelin basic protein of nerve axons. Recently, there has been growing interest in studying the role of a newly described population of immunity cells - innate lymphoid cells (ILCs) in the pathogenesis of the disease. At the same time, it was found that during pregnancy there is a weakening of Th1-mediated autoimmune pathologies manifestations, including MS. In this work, we studied phenotypic characteristics of ILC in MS patients in comparison with healthy donors after 48 h incubation with pregnancy hormone estriol (E3) and commensal microflora cells. To activate ILC, strains of Ecsherichia coli K12 and Lactobacillus plantarum 8R-A3 were used. ILC phenotype was assessed by flow cytometry using monoclonal antibody staining. It has been established that E3 and bacterial factors are able to regulate the maturation of ILC subtypes and their cytokines in different ways. In general, the studied factors influence the phenotypic changes in ILC cells, leading to the transition from one type to another, both in healthy donors and in MS patients.

Leptin regulates thymic plasmacytoid dendritic cell ability to influence the thymocyte distribution in vitro.

Leptin, the adipocyte-derived hormone, involved in regulating food intake and body weight, plays an important role in immunity and reproduction. Leptin signals via the specific membrane receptors expressed in most types of immune cells including dendritic cells (DCs) and thymocytes. Leptin enhances thymopoiesis and modulates T-cell-mediated immunity. Thymic plasmacytoid DCs (pDCs) are predominated in the thymus. They play an important role in thymocyte differentiation. We have analyzed whether leptin mediates its effects on human thymocytes by influencing on pDCs. We used leptin at concentration corresponding to its level during II-III trimesters of physiological pregnancy. We cultivated leptin-primed pDCs with autologous thymocytes and estimated the main thymocyte subsets expressing αß chains of the T-cell receptor (αßTCR), natural regulatory T-cells (tTreg), natural T-helpers producing interleukin-17 (nTh17) and invariant natural killer T-cells (iNKT) in vitro. We have shown that leptin augmented CD86, CD276 expressions and depressed IL-10 productions by pDCs. Leptin-primed pDCs decreased the percentage of CD4+CD8+αßTCR+ thymocytes, increased CD4hiCD8-/loαßTCR+ cells. pDCs cultivated with leptin decreased the number of iNKT precursors, and did not change the number of tTreg and nTh17 precursors. Thus, leptin's important role in regulation of thymic pDC abilities to influence on the thymocyte distribution was indicated in vitro.

Estriol in regulation of cell-mediated immune reactions in multiple sclerosis.

The effect of pregnancy hormone estriol (E3) on innate and adaptive immunity cells functions in patients with multiple sclerosis (MS) in comparison with healthy donors (HD) was studied. E3 inhibited phagocytic activity of neutrophils and enhanced monocytes IDO activity. Treg percentage increased and number of Th17 and iNKT cells decreased under E3 influence. At the same time, E3 stimulated production of IL-10 and inhibited secretion of IL-17. The hormonal effects were realized on the cells of both HD and MS patients. Thus, the MS amelioration during pregnancy may be related to E3 influence.

Effect of bacterial components of mixed culture supernatants of planktonic and biofilm Pseudomonas aeruginosa with commensal Escherichia coli on the neutrophil response in vitro.

Pseudomonas aeruginosa (PA) responsible for acute and chronic infections often forms a well-organized bacterial population with different microbial species including commensal strains of Escherichia coli. Bacterial extracellular components of mixed culture can modulate the influence of bacteria on the neutrophil functions. The objective of this study was to compare the effect of pyocyanin, pyoverdine, LPS, exopolysaccharide of single species and mixed culture supernatants of PA strains and E. coli K12 on microbicidal, secretory activity of human neutrophils in vitro. Bacterial components of E. coli K12 in mixed supernatants with 'biofilm' PA strains (PA ATCC, PA BALG) enhanced short-term microbicidal mechanisms and inhibited neutrophil secretion delayed in time. The influence of 'planktonic' PA (PA 9-3) exometabolites in mixed culture is almost mimicked by E. coli K12 effect on functional neutrophil changes. This investigation may help to understand some of the mechanisms of neutrophil response to mixed infections of different PA with other bacteria species.