Interleukin-17

Interleukin 17F
Crystallographic structure of dimeric human IL-17f.
Identifiers
Symbol	IL17F
Alt. symbols	ML-1
Entrez	112744
HUGO	16404
OMIM	606496
PDB	1JPY
RefSeq	NP_443104
UniProt	Q96PD4
Other data
Locus	Chr. 6 p12

Interleukin 17A (IL-17 or IL-17A), originally identified as a transcript from a rodent T-cell hybridoma by Rouvier et al. in 1993, is the founding member of a group of cytokines called the IL-17 family. Known as CTLA8 in rodents, IL-17 shows high homology to viral IL-17 encoded by an open reading frame of the T-lymphotropic rhadinovirus Herpesvirus saimiri.

Interleukin 17 is a pro-inflammatory cytokine produced by T-helper cells and is induced by IL-23. To elicit its functions, IL-17 binds to a type I cell surface receptor called IL-17R of which there are at least three variants IL17RA, IL17RB, and IL17RC. IL-17 acts as a potent mediator in delayed-type reactions by increasing chemokine production in various tissues. Signaling from IL-17 recruits monocytes and neutrophils to the site of inflammation in response to invasion by pathogens, similar to Interferon gamma. In promoting inflammation, IL-17 has been demonstrated to act synergistically with tumor necrosis factor and interleukin-1. This activity can also be redirected towards the host and result in various autoimmune disorders that involve chronic inflammation, such as the skin disorder psoriasis.

In addition to IL-17A, members of the IL-17 family include IL-17B, IL-17C, IL-17D, IL-17E (also called IL-25), and IL-17F. All members of the IL-17 family have a similar protein structure, with four highly conserved cysteine residues critical to their 3-dimensional shape, yet they have no sequence similarity to any other known cytokines. Phylogenetic analysis reveals that among IL-17 family members, the IL-17F isoforms 1 and 2 (ML-1) have the highest homology to IL-17A (sharing 55 and 40% amino acid identity to IL-17A respectively), followed by IL-17B (29%), IL-17D (25%), IL-17C (23%), and IL-17E being most distantly related to IL-17A (17%). These cytokines are all well conserved in mammals, with as much as 62–88% of amino acids conserved between the human and mouse homologs.