PMC

The differential production of IL-12 and IL-23 by dendritic cells determines the polarization of T_H1 and T_H17 cell differentiation. Increasing evidence from animal models and results of clinical trials indicate a key role for IL-23 and T_H17 cells in autoimmune-driven inflammation. The IL-12p40 antibodies under clinical development block both the IL-12 and IL-23 driven pathways. Awaited with interest is the more focused therapeutic targeting of the IL-23/T_H17 axis.

IL-6 acts via receptor complexes containing at least one subunit of gp130. A) Binding to the membrane-bound IL-6R. IL-6 first binds to the IL-6R on target cells, which in turn, associates with gp130, leading to dimerization of gp130 and subsequent intracellular signaling. The membrane bound IL-6R has restricted expression on hepatocytes, neutrophils, monocytes, macrophages, and a subset of T cells. B) Trans-signaling through the soluble IL-6 receptor (sIL-6R). sIL-6R derives from proteolysis of the transmembrane IL-6R or alternatively spliced transcripts. Many cells expressing only the gp130 complex are responsive to sIL-6R in the presence of IL-6. They include early hematopoietic progenitor cells, T cells, neural cells, smooth muscle cells, mesothelial cells, and endothelial cells (adapted from reference ).