Interleukin 17 - Receptors

Receptors

See also Interleukin-17 receptors.

The IL-17 receptor family consists of five, broadly distributed receptors (IL-17RA, B, C, D and E) that present with individual ligand specificities. Within this family of receptors, IL-17RA is the best-described. IL-17RA binds both IL-17A and IL-17F and is expressed in multiple tissues: vascular endothelial cells, peripheral T cells, B cell lineages, fibroblast, lung, myelomonocytic cells, and marrow stromal cells. Signal transduction for both IL-17A and IL-17F requires the presence of a heterodimeric complex consisting of both IL-17RA and IL-17RC and the absence of either receptor results in ineffective signal transduction. This pattern is reciprocated for other members of the IL-17 family such as IL-17E, which requires an IL-17RA-IL-17RB compex (also known as IL-17Rh1, IL-17BR or IL-25R) for effective function.

Another member of this receptor family, IL-17RB, binds both IL-17B and IL-17E. Furthermore, it is expressed in the kidney, pancreas, liver, brain, and intestine. IL-17RC is expressed by the prostate, cartilage, kidney, liver, heart, and muscle, and its gene may undergo alternate splicing to produce a soluble receptor in addition to its cell membrane-bound form. In similar manner, the gene for IL-17RD may undergo alternative splicing to yield a soluble receptor. This feature may allow these receptors to inhibit the stimulatory effects of their yet-undefined ligands. The least-described of these receptors, IL-17RE, is known to be expressed in the pancreas, brain, and prostate.

Signal transduction by these receptors is as diverse as their distribution. These receptors do not exhibit a significant similarity in extracellular or intracellular amino acid sequence when compared to other cytokine receptors. Transcription factors such as TRAF6, JNK, Erk1/2, p38, AP-1 and NF-κB have been implicated in IL-17 mediated signaling in a stimulation-dependent, tissue-specific manner. Other signaling mechanisms have also been proposed, but more work is needed to fully elucidate the true signaling pathways used by these diverse receptors.