Glomerulonephritis is traditionally considered to result from the invasion of the kidney by autoantibodies and immune complexes from the circulation or following their formation in situ, and by cells of the innate and the adaptive immune system. The inflammatory response leads to the proliferation and dysfunction of cells of the glomerulus, and invasion of the interstitial space with immune cells, resulting in tubular cell malfunction and fibrosis. T cells are critical drivers of autoimmunity and related organ damage, by supporting B-cell differentiation and antibody production or by directly promoting inflammation and cytotoxicity against kidney resident cells. T cells might become activated by autoantigens in the periphery and become polarized to secrete inflammatory cytokines before entering the kidney where they have the opportunity to expand owing to the presence of costimulatory molecules and activating cytokines. Alternatively, naive T cells could enter the kidney where they become activated after encountering autoantigen and expand locally. As not all individuals with a peripheral autoimmune response to kidney antigens develop glomerulonephritis, the contribution of local kidney factors expressed or produced by kidney cells is probably of crucial importance. Improved understanding of the biochemistry and molecular biology of T cells in patients with glomerulonephritis offers unique opportunities for the recognition of treatment targets for autoimmune kidney disease.

T cells and autoimmune kidney disease

Exploring the potential function of trace elements in human health: a therapeutic perspective

Plasticity in biological systems is attributed to the combination of multiple parameters which determine function. These include genotypic, phenotypic, and environmental factors. While biological processes can be viewed as ordered and sequential, biological randomness was suggested to underline part of them. The present review looks into the concept of randomness in biological systems by exploring the glycosphingolipids-NKT cells example. NKT cells are a unique subset of regulatory lymphocytes which play a role in both inflammation and tolerance. Glycosphingolipids promote an immune balance by changing different arms of the immune system in opposing environments. Traditional immunology looks at skewing the immune system into different directions by different types of activation of the same cell stimulation of different cells subsets, use of different ligands, or different the effect of different immune environments. While these may explain some of the effects, the lack of consistency and opposing results under similar settings may involve randomness which may also be part of real life effects of immunomodulatory agents. It means that several of the biological processes, cannot be explained by simple linear models, and may involve more complex concepts. The application for these concepts for improving therapies to patients with Gaucher disease are discussed.

SUMMARY 

The use of different ligands that target a variety of cell subsets in different immune environments may underlie differences in the functionality of NKT cells and their variability in response to NKT-based therapies. The novel concept of randomness in biology means that several biological processes cannot be solely explained by simple linear models and may instead involve much more complicated schemes of random disorder. These may have implications on future design of therapeutic regimens for improving the response to current treatments.

/pdf/b-glycosphingolipids-as-mediators-of-both-inflammation-and-1yd9djjvnr.pdf

β-Glycosphingolipids as Mediators of Both Inflammation and Immune Tolerance: A Manifestation of Randomness in Biological Systems.

Considering the implications of B, T, and natural killer (NK) cells in the pathophysiology of systemic autoimmune diseases, the assessment of their distribution in the blood could be helpful for physicians in the complex process of determining a precise diagnosis. In primary Sjogren's syndrome, transitional and active naive B cells are increased and memory B cells are decreased compared to healthy controls and other systemic diseases. However, their utility to improve the accuracy of classification criteria has not been proven. In early untreated rheumatoid arthritis, proportions of regulatory T cells are constantly reduced, but other patterns are difficult to determine given the heterogeneity of published studies. In systemic lupus erythematosus, the lack of studies using large cohorts of patients and the diversity of the possible pathological mechanisms involved are also important impediments. Nevertheless, transitional B cell and plasma cell proportions are increased in most of the studies, the CD4/CD8 ratio is decreased, and the number of NK cells is reduced. Despite the low number of studies, anomalies of lymphocyte subset distribution was also described in ANCA-associated vasculitis, systemic scleroderma, and myositis. For now, flow cytometric analysis of lymphocyte subsets has focused mainly on specific subpopulations and is more useful for basic and translational research than for diagnostics in clinical practice. However, new modern methods such as mass cytometry and bioinformatics analyses may offer the possibility to simultaneously account for the relative proportions of multiple lymphocyte subsets and define a global profile in homogeneous groups of patients. The years to come will certainly incorporate such global lymphocyte profiling in reclassification of systemic autoimmune diseases.

Could Lymphocyte Profiling be Useful to Diagnose Systemic Autoimmune Diseases

iNKT cells ameliorate human autoimmunity: Lessons from alopecia areata

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with different variety of clinical manifestations. Natural killer T (NKT) cells are innate lymphocytes that play a regulatory role during broad range of immune responses. A number of studies demonstrated that the quantity and quality of invariant NKT (iNKT) cells showed marked defects in SLE patients in comparison to healthy controls. This finding suggests that iNKT cells may play a regulatory role in the occurrence and development of this disease. In this review, we mainly summarized the most recent findings about the behavior of NKT cells in SLE patients and mouse models, as well as how NKT cells affect the proportion of T helper cells and the production of autoreactive antibodies in the progress of SLE. This will help people better understand the role of NKT cells in the development of SLE and improve the therapy strategy.

/pdf/immunoregulation-of-nkt-cells-in-systemic-lupus-rpr9dpunhr.pdf

Immunoregulation of NKT Cells in Systemic Lupus Erythematosus

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Immunoregulation of NKT Cells in Systemic Lupus Erythematosus