IL-17A was initially identified from a subtracted cDNA library between closely related murine lymphoid cells called CTLA-8. IL-17A shares 58% homology with an open reading frame of the T-lymphotropic Herpes virus Samirii virus (viral IL-17). IL-17A belongs to a family of cytokines, which has five members: designated IL-17A-F. IL-17 is expressed by a unique lineage of CD4 T cells known as Th17 cells. This lineage selectively produces proinflammatory cytokines including IL-17, IL-17F, IL-21, and IL-22. In mice, the differentiation of this new lineage is initiated by TGFbeta-1 and IL-6 or IL-21, which activates Stat3 and induces the expression of the transcription factor retinoic acid-related orphan receptors (RORγt and RORα). IL-23, which also activates Stat3, serves to maintain Th17 cells lineage.