NLRC5 is a member of the NLR family that acts as a transcriptional activator of MHC class I genes. In line with the function of several related NLR proteins in innate immune responses, there is, however, also ample evidence that NLRC5 contributes to innate and adaptive immune responses beyond the regulation of MHC class I genes. In human and murine cells, for example, NLRC5 was proposed to contribute to inflammatory and type I interferon responses. The role of NLRC5 in these and other cellular processes is hitherto still not well understood and blurred by discrepancies in the reported data. Here, we provide a detailed and critical discussion of the available experimental data on the emerging biological functions of NLRC5 in innate immune responses in men and mice. Better awareness of the multiple roles of NLRC5 will help to define its overall contribution to immune responses and cancer.

Application of dendritic cells (DCs) to prime responses to tumor Ags provides a promising approach to immunotherapy. However, only a limited number of DCs can be manufactured from adult precursors. In contrast, pluripotent embryonic stem (ES) cells represent an inexhaustible source for DC production, although it remains a major challenge to steer directional differentiation because ES cell-derived cells are typically immature with impaired functional capacity. Consistent with this notion, we found that mouse ES cell-derived DCs (ES-DCs) represented less mature cells compared with bone marrow-derived DCs. This finding prompted us to compare the gene expression profile of the ES cell- and adult progenitor-derived, GM-CSF-instructed, nonconventional DC subsets. We quantified the mRNA level of 17 DC-specific transcription factors and observed that 3 transcriptional regulators (Irf4, Spi-B, and Runx3) showed lower expression in ES-DCs than in bone marrow-derived DCs. In light of this altered gene expression, we probed the effects of these transcription factors in developing mouse ES-DCs with an isogenic expression screen. Our analysis revealed that forced expression of Irf4 repressed ES-DC development, whereas, in contrast, Runx3 improved the ES-DC maturation capacity. Moreover, LPS-treated and Runx3-activated ES-DCs exhibited enhanced T cell activation and migratory potential. In summary, we found that ex vivo-generated ES-DCs had a compromised maturation ability and immunogenicity. However, ectopic expression of Runx3 enhances cytokine-driven ES-DC development and acts as an instructive tool for the generation of mature DCs with enhanced immunogenicity from pluripotent stem cells.

Besides its well-known psychoactive effects, caffeine has a broad range of actions. It regulates several physiological mechanisms as well as modulates both native and adaptive immune responses by various ways. Although caffeine is assumed to be a negative regulator of inflammation, the effect on the secretion of pro- and anti-inflammatory cytokines is highly controversial. Macrophages are major mediators of inflammatory responses; however, the various subpopulations develop different effects ranging from the initiation to the resolution of inflammation. Here we report a comparative analysis of the effect of caffeine on two subpopulations of human monocyte-derived macrophages differentiated in the presence of macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF), resulting in M-MΦs and GM-MΦs, respectively. We showed that although TNF-α secretion was downregulated in both LPS-activated MΦ subtypes by caffeine, the secretion of IL-8, IL-6, and IL-1β as well as the expression of Nod-like receptors was enhanced in M-MΦs, while it did not change in GM-MΦs. We showed that caffeine (1) altered adenosine receptor expression, (2) changed Akt/AMPK/mTOR signaling pathways, and (3) inhibited STAT1/IL-10 signaling axis in M-MΦs. We hypothesized that these alterations play an important modulatory role in the upregulation of NLRP3 inflammasome-mediated IL-1β secretion in LPS-activated M-MΦs following caffeine treatment.

The vast majority of studies focusing on the effects of endurance exercise on hematological parameters and leukocyte gene expression were performed in adult men, so our aim was to investigate these changes in young females. Four young (age 15.3 ± 1.3 years) elite female athletes completed an exercise session, in which they accomplished the cycling and running disciplines of a junior triathlon race. Blood samples were taken immediately before the exercise, right after the exercise, and then 1, 2, and 7 days later. Analysis of cell counts and routine biochemical parameters was complemented by RNA sequencing (RNA-seq) to whole blood samples. The applied exercise load did not trigger remarkable changes in either cardiovascular or biochemical parameters; however, it caused a significant increase in the percentage of neutrophils and a significant reduction in the ratio of lymphocytes immediately after exercise. Furthermore, endurance exercise induced a characteristic gene expression pattern change in the blood transcriptome. Gene set enrichment analysis (GSEA) using the Reactome database revealed that the expression of genes involved in immune processes and neutrophil granulocyte activation was upregulated, while the expression of genes important in translation and rRNA metabolism was downregulated. Comparison of a set of immune cell gene signatures (ImSig) and our transcriptomic data identified 15 overlapping genes related to T cell functions, and involved in podosome formation and adhesion to the vessel wall. Our results suggest that RNA-seq to whole blood together with ImSig analysis are useful tools for investigation of systemic responses to endurance exercise.