In recent years, a significant increase in the frequency of disorders caused by air pollutants has been observed. Here we asked whether transition metal-containing particulate matter (TMCPM), a component of air pollution, has an effect on the activity of human CD4+ T cell subsets (Th1, Th2, Th17, and Treg). Peripheral blood mononuclear cells (PBMC) from healthy donors were cultured with or without NIST (SRM 1648a—standard urban particulate matter purchased from the National Institute for Standards and Technology) and LAP (SRM 1648a particulate matter treated within 120 min with cold oxygen plasma) preparations of TMCPM, differing in organic compounds content. Data show that TMCPM treatment increased the level of CD4+ cells positive for IFN-γ and IL-17A, specific for Th1 and Th17 cells, respectively. Moreover, a substantial decrease in frequency of Foxp3 positive CD4+ cells was observed in parallel. This effect was more pronounced for NIST particles, containing more organic components, including endotoxin (LPS - lipopolysaccharide) and required the presence of monocytes. Inactivation of LPS by treatment of TMCPM with polymyxin B reduced the inflammatory response of monocytes and Th subsets but did not abolish this activity, suggesting a role of their inorganic components. In conclusion, treatment of human PBMC with TMCPM skews the balance of Th1/Th2 and Treg/Th17 cells, promoting polarization of CD4+ T cells into Th1 and Th17 subsets. This phenomenon requires activation of monocytes and depends on the organic and inorganic fractions, including endotoxin content in TMCPM, as significantly higher inflammatory response was observed for the NIST comparing to LAP. This observation may shed a new light on the role of TMCPM in development and exacerbation of allergies, inflammatory, and autoimmune disorders.

Severe and/or recurrent infection with Herpes simplex virus (HSV) is observed in a large group of patients treated in clinical immunology facilities. Atypical and prolonged HSV infection is the most common clinical manifestation of disturbed NK cell development and functions, yet the molecular basis of these disorders is still largely unknown. Since recent findings indicated the importance of miRNA in regulating NK cell development, maturation and functions, the aim of our study was to investigate miRNA expression pattern in NK cells in patients with severe and/or recurrent infections with HSV and analyze the role of these miRNAs in NK cell antiviral response. As a result, miRNA expression pattern analysis of human best known 754 miRNAs revealed that patients with severe and/or recurrent HSV infection had substantially upregulated expression of four miRNAs: miR-27b, miR-199b, miR-369-3p and miR-491-3p, when compared to healthy controls. Selective inhibition of miR-27b, miR-199b, miR-369-3p and miR-491-3p expression in NK-92 cells resulted in profound upregulation of 4 genes (APOBEC3G, MAP2K3, MAVS and TLR7) and downregulation of 36 genes taking part in antiviral response or associated with signaling pathways of Toll-like receptors (TLR), NOD-like receptors, the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) and type I IFN-related response. Additionally, flow cytometry analysis revealed that miR-369-3p and miR-491-3p inhibitors downregulated NK cell intracellular perforin expression, while the expression of granzyme B and IFNγ remained unchanged. Taken together, our study suggests a novel mechanism which may promote recurrence and severity of HSV infection, based on miRNAs-dependent posttranscriptional regulation of genes taking part in antiviral response of human NK cells.

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Spondyloarthropathies (SpA) are a family of rheumatic disorders that could be divided into axial (axSpA) and peripheral (perSpA) sub-forms depending on the disease clinical presentation. The chronic inflammation is believed to be driven by innate immune cells such as monocytes, rather than self-reactive cells of adaptive immune system. The aim of the study was to investigate the micro-RNA (miRNA) profiles in monocyte subpopulations (classical, intermediate and non-classical subpopulations) acquired from SpA patients or healthy individuals in search for prospective disease specific and/or disease subtype differentiating miRNA markers. Several SpA-specific and axSpA/perSpA differentiating miRNAs have been identified that appear to be characteristic for specific monocyte subpopulation. For classical monocytes, upregulation of miR-567 and miR-943 was found to be SpA-specific, whereas downregulation of miR-1262 could serve as axSpA-differentiating, and the expression pattern of miR-23a, miR-34c, mi-591 and miR-630 as perSpA-differentiating markers. For intermediate monocytes, expression levels of miR-103, miR-125b, miR-140, miR-374, miR-376c and miR-1249 could be used to distinguish SpA patients from healthy donors, whereas the expression pattern of miR-155 was identified as characteristic for perSpA. For non-classical monocytes, differential expression of miR-195 was recognized as general SpA indicator, while upregulation of miR-454 and miR-487b could serve as axSpA-differentiating, and miR-1291 as perSpA-differentiating markers. Our data indicate for the first time that in different SpA subtypes, monocyte subpopulations bear disease-specific miRNA signatures that could be relevant for SpA diagnosis/differentiation process and may help to understand SpA etiopathology in the context of already known functions of monocyte subpopulations.

In this study, we report a 4-month-old boy with T−B+NK− severe combined immunodeficiency (SCID) due to a novel mutation in exon 2 of IL2RG, the gene encoding the interleukin (IL) common gamma chain (γc) of the cytokine receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. The patient was born from a twin pregnancy. He manifested recurrent infections of the gastrointestinal tract, whereas his twin brother was asymptomatic with no immune defects. In order to evaluate the effect of this unreported variant on the protein structure, a structural modeling process was performed showing prominent biochemical alterations of the protein features, including molecular weight, isoelectric charge, and possible changes to its secondary and tertiary structure.