Sarcoidosis is a systemic granulomatous disease that develops due to the Th1, Th17 and Treg lymphocytes disturbance. There is an assumption, that B cells and follicular T-helper (Tfh) cells may play an important role in this disorder, as well as in several other autoimmune diseases. The aim of this study was to determine CD19+ B cells subset distribution in the peripheral blood and to define disturbance in the circulating Tfh cells subsets in patients with sarcoidosis. The prospective comparative study was performed in 2016–2018, where peripheral blood B cell subsets and circulating Tfh cell subsets were analyzed in 37 patients with primarily diagnosed sarcoidosis and 35 healthy donors using multicolor flow cytometry. In the results of our study we found the altered distribution of peripheral B cell subsets with a predominance of “naïve” (IgD + CD27−) and activated B cell (Bm2 and Bm2′) subsets and a decreased frequency of memory cell (IgD+ CD27+ and IgD− CD27+) in peripheral blood of sarcoidosis patients was demonstrated. Moreover, we found that in sarcoidosis patients there are increased levels of B cell subsets, which were previously shown to display regulatory capacities (CD24+++ CD38+++ and CD5 + CD27−). Next, a significantly higher proportion of CXCR5-expressing CD45RA − CCR7+ Th cells in patients with sarcoidosis in comparison to the healthy controls was revealed, that represents the expansion of this memory Th cell subset in the disease. This is the first study to demonstrate the association between the development of sarcoidosis and imbalance of circulating Tfh cells, especially CCR4− and CXCR3-expressing Tfh subsets. Finally, based on our data we can assume that B cells and Tfh2- and Tfh17-like cells – most effective cell type in supporting B-cell activity, particularly in antibody production – may be involved in the occurrence and development of sarcoidosis and in several other autoimmune conditions. Therefore, we can consider these results as a new evidence of the autoimmune mechanisms in the sarcoidosis development.

The development of intravitreal glucocorticoid delivery systems is a current global challenge for the treatment of inflammatory diseases of the posterior segment of the eye. The main advantages of these systems are that they can overcome anatomical and physiological ophthalmic barriers and increase local bioavailability while prolonging and controlling drug release over several months to improve the safety and effectiveness of glucocorticoid therapy. One approach to the development of optimal delivery systems for intravitreal injections is the conjugation of low-molecular-weight drugs with natural polymers to prevent their rapid elimination and provide targeted and controlled release. This study focuses on the development of a procedure for a two-step synthesis of dexamethasone (DEX) conjugates based on the natural polysaccharide chitosan (CS). We first used carbodiimide chemistry to conjugate DEX to CS via a succinyl linker, and we then modified the obtained systems with succinic anhydride to impart a negative ζ-potential to the polymer particle surface. The resulting polysaccharide carriers had a degree of substitution with DEX moieties of 2–4%, a DEX content of 50–85 μg/mg, and a degree of succinylation of 64–68%. The size of the obtained particles was 400–1100 nm, and the ζ-potential was −30 to −33 mV. In vitro release studies at pH 7.4 showed slow hydrolysis of the amide and ester bonds in the synthesized systems, with a total release of 8–10% for both DEX and succinyl dexamethasone (SucDEX) after 1 month. The developed conjugates showed a significant anti-inflammatory effect in TNFα-induced and LPS-induced inflammation models, suppressing CD54 expression in THP-1 cells by 2- and 4-fold, respectively. Thus, these novel succinyl chitosan-dexamethasone (SucCS-DEX) conjugates are promising ophthalmic carriers for intravitreal delivery.

The main role in the control of tuberculosis infection is played by macrophages and Th1 and CD8+ T cells. The study aimed to identify the most diagnostically significant CD8+ T cell subsets in tuberculosis patients. Methods: Peripheral blood samples from patients with clinical, radiological, and bacteriologically confirmed pulmonary tuberculosis (TB, n = 32) and healthy subjects (HC, n = 31) were collected and analyzed using 10-color flow cytometry. Results: The frequency of the EM4 CD3+CD8+ cells was reduced in the peripheral blood of patients with pulmonary tuberculosis, while the relative and absolute number of EM1 CD3+CD8+ cells increased compared to the control group. CD57 expression was reduced in patients with pulmonary tuberculosis on EM1, EM2, and pE1 CD3+CD8+ cells, whereas the EM3 cells had a high level of CD57 expression. The relative and absolute number of Tc2 (CCR6–CXCR3–) cells in peripheral blood in patients with pulmonary tuberculosis was increased, while the frequency of Tc1 (CCR6–CXCR3+) was decreased, compared to healthy donors. Conclusions: Patients with pulmonary tuberculosis have an abnormal CD3+CD8+ cell profile and demonstrate their impaired maturation and functional activity.

The purpose of this study was to provide an immuno-mediated substantiation of the etiopathogenesis of mucositis and peri-implantitis based on the results of experimental, laboratory and clinical studies. The biopsy material was studied to identify impregnated nanoscale and microscale particles in the structure of pathological tissues by using X-ray microtomography and X-ray fluorescence analyses. Electron microscopy with energy-dispersive analysis identified the composition of supernatants containing nanoscale metal particles obtained from the surfaces of dental implants. The parameters of the nanoscale particles were determined by dynamic light scattering. Flow cytometry was used to study the effect of nanoscale particles on the ability to induce the activation and apoptosis of immunocompetent cells depending on the particles’ concentrations during cultivation with the monocytic cell line THP-1 with the addition of inductors. An analysis of the laboratory results suggested the presence of dose-dependent activation, as well as early and late apoptosis of the immunocompetent cells. Activation and early and late apoptosis of a monocytic cell line when THP-1 was co-cultured with nanoscale metal particles in supernatants were shown for the first time. When human venous blood plasma was added, both activation and early and late apoptosis had a dose-dependent effect and differed from those of the control groups.

The emission of nanoscale particles from the surfaces of dental implants leads to the cumulative effect of particle complexes in the bone bed and surrounding soft tissues. Aspects of particle migration with the possibility of their involvement in the development of pathological processes of systemic nature remain unexplored. The aim of this work was to study protein production during the interaction of immunocompetent cells with nanoscale metal particles obtained from the surfaces of dental implants in the supernatants. The ability to migrate nanoscale metal particles with possible involvement in the formation of pathological structures, in particular in the formation of gallstones, was also investigated. The following methods were used: microbiological studies, X-ray microtomography, X-ray fluorescence analysis, flow cytometry, electron microscopy, dynamic light scattering, and multiplex immunofluorescence analysis. For the first time, titanium nanoparticles in gallstones were identified by X-ray fluorescence analysis and electron microscopy with elemental mapping. The multiplex analysis method revealed that the physiological response of the immune system cells, in particular neutrophils, to nanosized metal particles significantly reduced TNF-a production both through direct interaction and through double lipopolysaccharide-induced signaling. For the first time, a significant decrease in TNF-a production was demonstrated when supernatants containing nanoscale metal particles were co-cultured with proinflammatory peritoneal exudate obtained from the peritoneum of the C57Bl/6J inbred mice line for one day.

Acute disorders of cerebral circulation are one of the leading problems of modern clinical medicine, due to their significant spread in the human population and the extremely negative impact exerted on the patient’s body. Currently available data allow us to talk about the multi-vector nature of the pathogenesis of ischemic brain damage. Within the framework of the cascade of developing pathochemical and pathophysiological processes, an essential role in the formation of ischemic stroke belongs to the inflammatory reaction occurring through the immune system’s response to cerebral tissue ischemia. One of the places of its implementation is the vessel wall located in the ischemic zone, where monocytes and neutrophils are attracted with the help of cell adhesion proteins. Complement activation plays a significant role, carried out mainly due to the C3 component or during the initialization of the mannose pathway. Activation of microglia and astrocytes plays a huge role directly in the focus of ischemia. It should be noted that in the process of activation, both microglia and astrocytes are able to acquire a pro-inflammatory or anti-inflammatory phenotype. The prevalence of the pro-inflammatory variant contributes to prolonged damage to brain tissue, while the predominance of the anti-inflammatory phenotype has a protective effect. An important role is played by a violation of the function of the blood-brain barrier, which provides an additional influx of leukocytes to the site of ischemia. In addition, individual subpopulations of T-lymphocytes penetrating through the damaged barrier also play a significant role in the organization and dynamics of the immuno-inflammatory response. The action of Th1 and Th2 cells, gamma-delta T lymphocytes, natural killer cells, as well as regulatory T lymphocytes has been most studied. The role of B-lymphocytes in the formation of a stroke focus is considered.