Editorial: Shaping of Human Immune System and Metabolic Processes by Viruses and Microorganisms

Conclusions In conclusion, articles in this Research Topic made a very significant contribution to our understanding of the role played by environmental factors, dysbiotic conditions, and infections in triggering diseases. Since this is a rapidly expanding area of research, many other factors contributing to the onset of these diseases are not covered here. We are confident, however, that further studies will expand the list as well as bring a better understanding of mechanisms involved in the onset of autoimmune and autoinflammatory diseases. Author Contributions All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication. Funding This study was supported by research funding from the Russian Science Foundation (No. 17-15-01099). Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Acknowledgments We are thankful to Simone Forest and Genevieve Michel for secretarial assistance. References Arleevskaya, M. I., Albina, S., Larionova, R. V., Gabdoulkhakova, A. G., Lemerle, J., and Renaudineau, Y. (2018). Prevalence and incidence of upper respiratory tract infection events are elevated prior to the development of rheumatoid arthritis in first-degree relatives. Front. Immunol. 9:2771. doi: 10.3389/fimmu.2018.02771 PubMed Abstract | CrossRef Full Text | G...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research

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Conclusion Our work establishes a TPE instrument and measurement method for noninvasive metabolic assessment of the human retina. This approach opens the possibility for monitoring eye diseases in the earliest stages before structural damage to the retina occurs.Funding NIH, Research to Prevent Blindness, Foundation for Polish Science, European Regional Development Fund, Polish National Agency for Academic Exchange, and Polish Ministry of Science and Higher Education.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
T cell polyfunctionality is a hallmark of protective immunity against pathogens and cancer, yet the molecular mechanism governing it remains mostly elusive. We found that canonical Wnt agonists inhibited human memory CD8+ T cell differentiation while simultaneously promoting the generation of highly polyfunctional cells. Downstream effects of Wnt activation persisted after removal of the drug, and T cells remained polyfunctional following subsequent cell division, indicating the effect is epigenetically regulated. Wnt activation induced a gene expression pattern that is enriched with stem cell–specific gene signature...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Tertiary lymphoid tissues (TLTs) facilitate local T and B cell interactions in chronically inflamed organs. However, the cells and molecular pathways that govern TLT formation are poorly defined. Here, we identified TNF superfamily CD153/CD30 signaling between 2 unique age-dependent lymphocyte subpopulations, CD153+PD-1+CD4+ senescence-associated T (SAT) cells and CD30+T-bet+ age-associated B cells (ABCs), as a driver for TLT expansion. SAT cells, which produced ABC-inducing factors IL-21 and IFN-γ, and ABCs progressively accumulated within TLTs in aged kidneys after injury. Notably, in kidney injury models, CD153 or...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
In this study, we report that osteoclast precursors (OPs) can function as a premetastatic niche component that facilitates breast cancer (BCa) bone metastasis at early stages. At the molecular level, unbiased GPCR ligand/agonist screening in BCa cells suggested that R-spondin 2 (RSPO2) and RANKL, through interaction with their receptor LGR4, promoted osteoclastic premetastatic niche formation and enhanced BCa bone metastasis. This was achieved by RSPO2/RANKL-LGR4 signal modulating the WNT inhibitor DKK1 through Gαq and β-catenin signaling. DKK1 directly facilitated OP recruitment through suppression of its recep...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
As cancers progress, they produce a local environment that acts to redirect, paralyze, exhaust, or otherwise evade immune detection and destruction. The tumor microenvironment (TME) has long been characterized as a metabolic desert, depleted of essential nutrients such as glucose, oxygen, and amino acids, that starves infiltrating immune cells and renders them dysfunctional. While not incorrect, this perspective is only half the picture. The TME is not a metabolic vacuum, only consuming essential nutrients and never producing by-products. Rather, the by-products of depleted nutrients, “toxic” metabolites in the...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Inborn errors of nucleic acid metabolism often cause aberrant activation of nucleic acid sensing pathways, leading to autoimmune or autoinflammatory diseases. The SKIV2L RNA exosome is cytoplasmic RNA degradation machinery that was thought to be essential for preventing the self-RNA–mediated interferon (IFN) response. Here, we demonstrate the physiological function of SKIV2L in mammals. We found that Skiv2l deficiency in mice disrupted epidermal and T cell homeostasis in a cell-intrinsic manner independently of IFN. Skiv2l-deficient mice developed skin inflammation and hair abnormality, which were also observed in a ...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Autophagy selectively degrades aggregation-prone misfolded proteins caused by defective cellular proteostasis. However, the complexity of autophagy may prevent the full appreciation of how its modulation could be used as a therapeutic strategy in disease management. Here, we define a molecular pathway through which recombinant IL-1 receptor antagonist (IL-1Ra, anakinra) affects cellular proteostasis independently from the IL-1 receptor (IL-1R1). Anakinra promoted H2O2-driven autophagy through a xenobiotic sensing pathway involving the aryl hydrocarbon receptor that, activated through the indoleamine 2,3-dioxygenase 1-kynur...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Suppressing inflammation has been the primary focus of therapies in autoimmune rheumatic diseases (AIRDs), including rheumatoid arthritis and systemic lupus erythematosus. However, conventional therapies with low target specificity can have effects on cell metabolism that are less predictable. A key example is lipid metabolism; current therapies can improve or exacerbate dyslipidemia. Many conventional drugs also require in vivo metabolism for their conversion into therapeutically beneficial products; however, drug metabolism often involves the additional formation of toxic by-products, and rates of drug metabolism can be ...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
BACKGROUND The temporal clustering of a cancer diagnosis with dermatomyositis (DM) onset is strikingly associated with autoantibodies against transcriptional intermediary factor 1-γ (TIF1-γ). Nevertheless, many patients with anti–TIF1-γ antibodies never develop cancer. We investigated whether additional autoantibodies are found in anti–TIF1-γ–positive patients without cancer.METHODS Using a proteomic approach, we defined 10 previously undescribed autoantibody specificities in 5 index anti–TIF1-γ–positive DM patients without cancer. These were subsequently examined...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Peanut oral immunotherapy (OIT) was recently approved by the US FDA. However, not all patients respond to OIT, and there is a high likelihood of regaining sensitization to peanuts after cessation of treatment. It is important, therefore, to identify biomarkers that impact and predict OIT outcomes. In this issue of the JCI, Monian, Tu, and colleagues describe distinct subsets of peanut-reactive CD4+ Th cell phenotypes and gene signatures with relevance to OIT outcomes using single-cell RNA-Seq and paired T cell receptor (TCR) α/β sequencing. The insights obtained will inform the development of therapeutics that t...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
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