[Show abstract][Hide abstract] ABSTRACT: Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are associated with systemic inflammation and acquired immunodeficiency, which promote cardiovascular disease, body wasting, and infections as leading causes of death. This phenomenon persists despite dialysis-related triggers of immune deregulation having been largely eliminated. Here we propose a potential immunoregulatory role of the intestinal microbiota in CKD/ESRD. We discuss how the metabolic alterations of uremia favor pathogen overgrowth (dysbiosis) in the gut and an increased translocation of living bacteria and bacterial components. This process has the potential to activate innate immunity and systemic inflammation. Persistent innate immune activation involves the induction of immunoregulatory mediators that suppress innate and adaptive immunity, similar to the concept of 'endotoxin tolerance' or 'immune paralysis' in advanced sepsis or chronic infections. Renal science has largely neglected the gut as a source of triggers for CKD/ESRD-related immune derangements and complications and lags behind on the evolving microbiota research. Interdisciplinary research activities at all levels are needed to unravel the pathogenic role of the intestinal microbiota in kidney disease and to evaluate if therapeutic interventions that manipulate the microbiota, such as pre- or probiotics, have a therapeutic potential to correct CKD/ESRD-related immune deregulation and to prevent the associated complications.Kidney International advance online publication, 16 January 2013; doi:10.1038/ki.2012.440.
Kidney International 01/2013; 83(6). DOI:10.1038/ki.2012.440 · 8.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent studies highlight an important role of the aryl hydrocarbon receptor (AhR) at mucosal barriers. Surprisingly, activation of the AhR, required for the maintenance of lymphocytes as well as lymphoid architecture, can be achieved via cues derived from the external environment. This environment contains both beneficial and harmful microorganisms as well as a diverse array of compounds, and the epithelia must offer very sophisticated levels of defence. This is achieved via multifaceted immune recognition diversity and cellular complexity. Mucosal associated tissues, particularly in the gastrointestinal tract, constitute a complex immune organ for local lymphocytes and contain highly organised lymphoid structures. We will discuss the recent observations concerning the AhR in relation to the function and maintenance of innate T cells, with focus on γδ T cells found enriched at epithelial barriers.
Seminars in Immunopathology 09/2013; 35(6). DOI:10.1007/s00281-013-0389-1 · 7.75 Impact Factor
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