Title:Targeting IL-17 and IL-23 in Immune Mediated Renal Disease
Volume: 22
Issue: 38
Author(s): Joanna R. Ghali, Stephen R. Holdsworth and A. Richard Kitching
Affiliation:
Keywords:
Acute kidney injury, anti-glomerular basement membrane disease, anti-neutrophil cytoplasmic antibody
associated vasculitis, interleukin 17, interleukin 12p40, systemic lupus erythematosus, Th17 cell.
Abstract: 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.
