Rola monocytów w patogenezie przewlekłej białaczki limfocytowej

Chronic lymphocytic leukemia (CLL) is one of the most common leukemias in adults. CLL is characterized by numerous immune disorders leading to the development of infections which have become the major cause of death in this group of patients. According to recent reports, many of immune alterations observed in the course of CLL could be attributed to dysfunctions of monocytes/macrophages and other cells of myeloid linage. In this article, we summarized the data on the role of monocytes and monocyte-derived cells in the pathogenesis of CLL

Collaborating with the Enemy: Function of Macrophages in the Development of Neoplastic Disease

Due to the profile of released mediators (such as cytokines, chemokines, growth factors, etc.), neoplastic cells modulate the activity of immune system, directly affecting its components both locally and peripherally. This is reflected by the limited antineoplastic activity of the immune system (immunosuppressive effect), induction of tolerance to neoplastic antigens, and the promotion of processes associated with the proliferation of neoplastic tissue. Most of these responses are macrophages dependent, since these cells show proangiogenic properties, attenuate the adaptive response (anergization of naïve T lymphocytes, induction of Treg cell formation, polarization of immune response towards Th2, etc.), and support invasion and metastases formation. Tumor-associated macrophages (TAMs), a predominant component of leukocytic infiltrate, “cooperate” with the neoplastic tissue, leading to the intensified proliferation and the immune escape of the latter. This paper characterizes the function of macrophages in the development of neoplastic disease

The short-term and long-term effects of intranasal mesenchymal stem cell administration to noninflamed mice lung

Mesenchymal stem cells (mesenchymal stromal cells; MSC)-based therapies remain a promising approach to treat degenerative and inflammatory diseases. Their beneficial effects were confirmed in numerous experimental models and clinical trials. However, safety issues concerning MSCs’ stability and their long-term effects limit their implementation in clinical practice, including treatment of respiratory diseases such as asthma, chronic obstructive pulmonary disease, and COVID-19. Here, we aimed to investigate the safety of intranasal application of human adipose tissue-derived MSCs in a preclinical experimental mice model and elucidate their effects on the lungs. We assessed short-term (two days) and long-term (nine days) effects of MSCs administration on lung morphology, immune responses, epithelial barrier function, and transcriptomic profiles. We observed an increased frequency of IFNγ- producing T cells and a decrease in occludin and claudin 3 as a long-term effect of MSCs administration. We also found changes in the lung transcriptomic profiles, reflecting redox imbalance and hypoxia signaling pathway. Additionally, we found dysregulation in genes clustered in pattern recognition receptors, macrophage activation, oxidative stress, and phagocytosis. Our results suggest that i.n. MSCs administration to noninflamed healthy lungs induces, in the late stages, low-grade inflammatory responses aiming at the clearance of MSCs graft

Surgical Treatment of Wounds Using Stem Cells in Epidermolysis Bullosa (EB)

Epidermolysis bullosa (EB) is a group of hereditary skin diseases, or genodermatoses, characterized by the formation of severe, chronic blisters with painful and life-threatening complications. Despite the previous and ongoing progress in the field, there are still no effective causative treatments for EB. The treatment is limited to relieving symptoms, which—depending on disease severity—may involve skin (blisters, poorly healing wounds caused by the slightest mechanical stimuli, contractures, scarring, pseudosyndactyly) and internal organ abnormalities (esophageal, pyloric, or duodenal atresia; renal failure; and hematopoietic abnormalities). The last decade saw a series of important discoveries that paved the way for new treatment methods, including gene therapy, bone marrow transplantation, cell therapy (allogenic fibroblasts, mesenchymal stem cells [MSCs], and clinical use of induced pluripotent stem cells. Tissue engineering experts are attempting to develop skin-like structures that can facilitate the process of healing to promote skin reconstruction in injuries that are currently incurable. However, this is incredibly challenging, due to the complex structure and the many functions of the skin. Below, we characterize EB and present its potential treatment methods. Despite the cure for EB being still out of reach, recent data from animal models and initial clinical trials in humans have raised patients’, clinicians’, and researchers’ expectations. Consequently, modifying the course of the disease and improving the quality of life have become possible. Moreover, the conclusions drawn based on EB treatment may considerably improve the treatment of other genetic diseases

Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19.

Rhinoviruses and allergens, such as house dust mite are major agents responsible for asthma exacerbations. The influence of pre-existing airway inflammation on the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely unknown. We analyse mechanisms of response to viral infection in experimental in vivo rhinovirus infection in healthy controls and patients with asthma, and in in vitro experiments with house dust mite, rhinovirus and SARS-CoV-2 in human primary airway epithelium. Here, we show that rhinovirus infection in patients with asthma leads to an excessive RIG-I inflammasome activation, which diminishes its accessibility for type I/III interferon responses, leading to their early functional impairment, delayed resolution, prolonged viral clearance and unresolved inflammation in vitro and in vivo. Pre-exposure to house dust mite augments this phenomenon by inflammasome priming and auxiliary inhibition of early type I/III interferon responses. Prior infection with rhinovirus followed by SARS-CoV-2 infection augments RIG-I inflammasome activation and epithelial inflammation. Timely inhibition of the epithelial RIG-I inflammasome may lead to more efficient viral clearance and lower the burden of rhinovirus and SARS-CoV-2 infections

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Trained Immunity as a Trigger for Atherosclerotic Cardiovascular Disease—A Literature Review

Atherosclerosis remains the leading cause of cardiovascular diseases and represents a primary public health challenge. This chronic state may lead to a number of life-threatening conditions, such as myocardial infarction and stroke. Lipid metabolism alterations and inflammation remain at the forefront of the pathogenesis of atherosclerotic cardiovascular disease, but the overall mechanism is not yet fully understood. Recently, significant effects of trained immunity on atherosclerotic plaque formation and development have been reported. An increased reaction to restimulation with the same stimulator is a hallmark of the trained innate immune response. The impact of trained immunity is a prominent factor in both acute and chronic coronary syndrome, which we outline in this review