Article

The immune system and kidney disease: basic concepts and clinical implications.

1] Institutes of Molecular Medicine and Experimental Immunology (IMMEI), Rheinische Friedrich-Wilhelms-Universität, Sigmund-Freud-Str. 25, 53105 Bonn, Germany. [2].
Nature Reviews Immunology (Impact Factor: 32.25). 09/2013; DOI: 10.1038/nri3523
Source: PubMed

ABSTRACT The kidneys are frequently targeted by pathogenic immune responses against renal autoantigens or by local manifestations of systemic autoimmunity. Recent studies in rodent models and humans have uncovered several underlying mechanisms that can be used to explain the previously enigmatic immunopathology of many kidney diseases. These mechanisms include kidney-specific damage-associated molecular patterns that cause sterile inflammation, the crosstalk between renal dendritic cells and T cells, the development of kidney-targeting autoantibodies and molecular mimicry with microbial pathogens. Conversely, kidney failure affects general immunity, causing intestinal barrier dysfunction, systemic inflammation and immunodeficiency that contribute to the morbidity and mortality of patients with kidney disease. In this Review, we summarize the recent findings regarding the interactions between the kidneys and the immune system.

0 Bookmarks
 · 
110 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The immune system is an important guardian of tissue homeostasis. In response to injury, resident and infiltrating immune cells orchestrate all phases of danger control, resolution of inflammation and tissue regeneration or scar formation. As mammalian postnatal kidneys are not capable of de novo nephrogenesis, recovery is limited to the regeneration or repair of existing nephrons. The regenerative capacity of the nephron varies between compartments; the epithelial cells of the tubule regenerate more efficiently than the structurally highly organized podocytes. Cells of the surrounding environment modulate nephron regeneration by secreting paracrine mediators. This Review discusses immune mediators and pathways that regulate the intrinsic regenerative capacity of the nephron. Eliminating injurious triggers, modulating renal inflammation and specifically enhancing the regenerative capacity of nephrons might be a promising strategy to improve long-term outcomes in patients with acute kidney injury and/or chronic kidney disease.
    Nature Reviews Nephrology 04/2014; · 7.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Interleukin (IL)-1β contributes to renal injury in immune complex glomerulonephritis. However, production of mature IL-1β depends on activation of the inflammasome that cleaves pro-IL-1β into its secretable form. A functional role of the NLRP3-containing inflammasome, which responds to various endogenous danger signals, was found in tubulointerstitial nephropathies, but its function in glomerular disease has not been established. To determine whether NLRP3 and its adapter molecule ASC contribute to glomerulonephritis, we induced T-cell-dependent autologous nephrotoxic serum nephritis in Nlrp3- and Asc-deficient mice. Renal expression of NLRP3/ASC inflammasome components and pro-IL-1β increased during nephrotoxic serum nephritis and was abundant in renal dendritic cells. This was associated with renal production of mature IL-1β, indicating inflammasome activation. Nlrp3 and Asc deficiency significantly attenuated glomerular injury, renal leukocyte infiltration, and T-cell activation. Production of mature IL-1β was abrogated in Asc-deficient mice, consistent with a loss of inflammasome-dependent IL-1β activation. Surprisingly, renal IL-1β secretion remained intact in Nlrp3-deficient mice, indicating noncanonical pro-inflammatory effects of NLRP3 in autologous nephrotoxic serum nephritis. This may include NLRP3-mediated glomerular release of pro-inflammatory high-mobility group box 1 protein as a noncanonical function of NLRP3/ASC in glomerulonephritis. Thus, therapeutic blockade of the NLRP3/ASC/IL-1β axis may be beneficial in glomerulonephritis.Kidney International advance online publication, 7 May 2014; doi:10.1038/ki.2014.161.
    Kidney International 05/2014; · 8.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The phagocytes of the innate immune system, macrophages and neutrophils, contribute to antibacterial defense, but their functional specialization and cooperation is unclear. Here, we report that three distinct phagocyte subsets play highly coordinated roles in bacterial urinary tract infection. Ly6C(-) macrophages acted as tissue-resident sentinels that attracted circulating neutrophils and Ly6C(+) macrophages. Such Ly6C(+) macrophages played a previously undescribed helper role: once recruited to the site of infection, they produced the cytokine TNF, which caused Ly6C(-) macrophages to secrete CXCL2. This chemokine activated matrix metalloproteinase-9 in neutrophils, allowing their entry into the uroepithelium to combat the bacteria. In summary, the sentinel macrophages elicit the powerful antibacterial functions of neutrophils only after confirmation by the helper macrophages, reminiscent of the licensing role of helper T cells in antiviral adaptive immunity. These findings identify helper macrophages and TNF as critical regulators in innate immunity against bacterial infections in epithelia.
    Cell 01/2014; 156(3):456-68. · 31.96 Impact Factor