TY - JOUR
T1 - Targeting IL-17 and IL-23 in immune mediated renal disease
AU - Ghali, Joanna
AU - Holdsworth, Stephen Roger
AU - Kitching, Arthur Richard
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
UR - http://www.eurekaselect.com/136326/article
U2 - 10.2174/0929867322666151030163022
DO - 10.2174/0929867322666151030163022
M3 - Article
SN - 0929-8673
VL - 22
SP - 4341
EP - 4365
JO - Current Medicinal Chemistry
JF - Current Medicinal Chemistry
IS - 38
ER -