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T helper (Th) cells belong to the adaptive immune system and provide an effective and antigen-specific means of host protection. Th17 cells are a subset of Th cells, characterized by the production of the inflammatory cytokines interleukin (IL)-17A (IL-17A) and IL-17F, which bind to a receptor complex comprised of IL-17RA and IL-17RC subunits. Th17 cells combat extracellular and fungal infections, but have been implicated in autoimmune diseases. In many autoimmune conditions, the dysregulated immune response involves several parts of the immune system, including autoantibodies, B and T cells. Targeted biological therapies are appealing, as they may prevent unwanted side effects in patients. There is evolving evidence that Th17 cells are important in the kidney, mediating injury in response to vascular or chemical insults to the renal tubules, and in autoimmune diseases of the glomerulus, either through a specific attack on the glomerular basement membrane or as part of a generalized systemic inflammatory disease. Therapies targeting IL-17A, IL-12p40 and IL-17RA are being explored in clinical trials or are being utilized in clinical practice for the treatment of other IL-17 mediated diseases, such as psoriasis. This review explores the current evidence that IL-17A and Th17 cells may be pathogenic in immune kidney disease, including anti-glomerular basement membrane disease, antineutrophil cytoplasmic antibody associated vasculitis and lupus nephritis, as well as in acute kidney injury. It will discuss the place that biological agents against IL-17A, IL-12p40 and IL-17RA may have in the treatment of these conditions.

Inflammation of blood vessels (vasculitis) results from many pathological processes and is found in many different diseases. However, in most situations, the pathological processes inducing vasculitis are unknown. The discovery of anti-neutrophil cytoplasmic autoantibodies (ANCAs) in the 1980s opened the door for studies that eventually led to the description of a new previously undescribed disease, ANCA-associated vasculitis (AAV). Unravelling the immunopathogenesis of this new disease resulted largely from the development of animal models. The major breakthroughs were the description of ANCA, its association with small vessel vasculitis and the discovery of its target autoantigens (myeloperoxidase and Proteinase 3). Three major disease syndromes comprise the AAVs, microscopic polyangiitis, granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis (EGPA). Recent human studies suggest that proteinase 3 and myeloperoxidase associated vasculitis are two separate but related diseases. The ability to induce murine autoimmunity to myeloperoxidase including ANCA (with the same immune staining patterns as human ANCA) and the capacity of this anti-myeloperoxidase autoimmunity to induce disease with many of the characteristic features of human AAV are well developed. However, the development of animal models of anti-proteinase 3 ANCA and EGPA is much less well developed. Animal models are important in understanding the human disease and in particular in defining potential therapeutic targets and in early stage therapeutic testing of potential drugs. Clearly the relevance of animal models depends on how closely they mimic human diseases. The current status of animal models of vasculitis will be described in detail with reference to these criteria.