[8] Lymphocytes including CD4+, CD8+, gamma-delta T (γδ-T), invariant NKT and innate lymphoid cells (ILCs) are primary sources of IL-17A.

[12] IL-17A receptor A (IL-17RA) was first isolated and cloned from mouse EL4 thymoma cells and the bioactivity of IL-17A was confirmed by stimulating the transcriptional factor NF-kappa B activity and interleukin-6 (IL-6) secretion in fibroblasts.

[14] High levels of this cytokine are associated with several chronic inflammatory diseases including rheumatoid arthritis, psoriasis and multiple sclerosis.

[6] Multiple sclerosis (MS) is a neurological disease caused by immune cells, which attack and destroy the myelin sheath that insulates neurons in the brain and spinal cord.

[15][16] More current experiments on this animal model have also revealed that a key function of IL-17A in central nervous system (CNS) autoimmunity was to recruit IL-1β-secreting myeloid cells.

[18][19] Human TH17 cells have been shown to efficiently transmigrate across the blood-brain barrier in multiple sclerosis lesions, promoting central nervous system inflammation.

[20] Psoriasis is an auto-inflammatory skin disease characterized by circumscribed, crimson red, silver-scaled, plaque-like inflammatory lesions.

Th17 cells infiltrate massively to the inflamed tissue of IBD patients and both in vitro and in vivo studies have shown that Th17-related cytokines may initiate and amplify multiple pro-inflammatory pathways.

[29][30] Nonetheless, Th17 signature cytokines, such as IL-17A and IL-22, may target gut epithelial cells and promote the activation of regulatory pathways and confer protection in the gastrointestinal tract.

[31][32] To this end, recent clinical trials targeting IL-17A in IBD were negative and actually showed increased adverse events in the treatment arm.

[34] It has been reported that serum IL-17 levels are also elevated in SLE patients compared to controls[35][36] and the Th17 pathway has been shown to drive autoimmune responses in pre-clinical mouse models of lupus.

[48] Animal studies have shown that cigarette smoke promotes pathogenic Th17 differentiation and induces emphysema,[49] while blocking IL-17A using neutralizing antibody significantly decreased neutrophil recruitment and the pathological score of airway inflammation in tobacco-smoke-exposed mice.

[63] Furthermore, immunization with pneumococcal whole cell antigen and several derivatives provided IL-17-mediated, but not antibody dependent, protection against S. pneumoniae challenge.

[70] IL-17A seemed to facilitate development of colorectal carcinoma by fostering angiogenesis via promote VEGF production from cancer cells[71] and it has been shown that IL-17A also mediates tumor resistance to anti-VEGF therapy through the recruitment of MDSCs.

[72] However IL-17A KO mice were more susceptible to developing metastatic lung melanoma,[73] suggesting that IL-17A can possibly promote the production of the potent antitumor cytokine IFN-γ, produced by cytotoxic T cells.