MORPHOMETRIC STUDY OF ARTERIES OF THE LOWER JAW REORGANIZATION ASPECTS IN THE SIMULATED POST-RESECTION ARTERIAL PULMONARY HYPERTENSION

Summary. The salivary glands are a special group of secretory organs that play a significant role in dental health of the population, as well as one of the vital functions of the whole human body. With the development of modern medical science, clinicians have often diagnosed salivary gland pathology. One of the most important problems of these pathologies is the study of direct and reverse effects of organs on each other, the principles of their correlations and methods of morphological expression. In recent decades, there has also been an increase of pulmonary lesions, which are accompanied by hypertension in the small circulation and lead to the development of pulmonary heart disease and its decompensation. There are isolated studies on the features of the involvement of the mandibular gland in the pathological process, and only some works reflect the structural changes of the submandibular gland in hemodynamic disorders. The aim of the work – to study morphometric aspects of mandibular arteries reorganization in simulated post-resection arterial pulmonary hypertension. Material and Methods. The arteries of medium (51–125) μm and small (26–50) μm calibers [16] of the mandibular salivary gland of 27 Vietnamese pigs, which were divided into 3 groups, were studied by a complex of histological and morphometric methods. Group 1 included 9 intact animals aged 6.5–7 months, group 2 – 12 pigs of the same age with post-resection pulmonary hypertension and compensated pulmonary heart, group 3 – 6 animals 6.5–7 months with pulmonary hypertension and decompensated pulmonary heart. Results and Discussion. Hypertension (one-month term) in the small circle of blood circulation, which occurred after right-sided pulmonectomy led to the development of pulmonary heart and venous stasis in the organs of the large circle of blood circulation, including in the mandibular gland. At arterial hypertension in a small circle of blood circulation essential structural reorganization of arteries of a mandibular gland is revealed. Although morphological changes were found in the arteries of small caliber of the studied organ and in the decompensation of the pulmonary heart. Conclusions. Our morphological study provided comprehensive information on the features of remodeling of the mandibular arteries in postresection arterial pulmonary hypertension. Prolonged pulmonary hypertension leads to structural rearrangement of the arteries of the middle and small caliber of the mandible, which is characterized by thickening of the membrane, narrowing their lumen and endothelial cells damage, impaired blood supply and hypoxia in the body. The biggest changes are in the arteries of the small caliber of the mandibular gland and in the decompensation of the pulmonary heart in 6.5–7 month old male pigs of the Vietnamese breed.

Circulating follicular helper T cells are increased in systemic sclerosis and promote plasmablast differentiation through the IL-21 pathway which can be inhibited by ruxolitinib

ObjectivesSystemic sclerosis (SSc) is an autoimmune disease characterised by widespread fibrosis, microangiopathy and autoantibodies. Follicular helper T (Tfh) cells CD4+CXCR5+PD-1+ cooperate with B lymphocytes to induce the differentiation of plasmocytes secreting immunoglobulins (Ig). Circulating Tfh (cTfh) cells are increased in several autoimmune diseases. However, there are no data about cTfh cells and their interaction with B cells in SSc. The aim of this study was to perform a quantitative and functional analysis of cTfh cells in SSc.MethodsUsing flow cytometry, we analysed cTfh cells from 50 patients with SSc and 32 healthy controls (HC). In vitro coculture experiments of sorted cTfh and B cells were performed for functional analysis. IgG and IgM production were measured by ELISA.ResultsWe observed that cTfh cell numbers are increased in patients with SSc compared with HC. Furthermore, the increase in cTfh cells was more potent in patients with severe forms of SSc such as diffuse SSc and in the presence of arterial pulmonary hypertension. cTfh cells from patients with SSc present an activated Tfh phenotype, with high expression of BCL-6, increased capacity to produce IL-21 in comparison with healthy controls. In vitro, cTfh cells from patients with SSc had higher capacity to stimulate the differentiation of CD19+CD27+CD38hi B cells and their secretion of IgG and IgM through the IL-21 pathway than Tfh cells from healthy controls. Blocking IL-21R or using the JAK1/2 inhibitor ruxolitinib reduced the Tfh cells’ capacity to stimulate the plasmablasts and decreased the Ig production.ConclusionsCirculating Tfh cells are increased in SSc and correlate with SSc severity. The IL-21 pathway or JAK1/2 blockade by ruxolitinib could be a promising strategy in the treatment of SSc.