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Interleukin-17 in inflammatory skin disorders

Author: Anoma Ranaweera, Medical Writer, Auckland, New Zealand. DermNet New Zealand Editor in Chief: A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand. Copy edited by Gus Mitchell. October 2019.

What is interleukin-17?

Interleukin (IL)-17 refers to a family of proteins that play critical roles against bacterial infections and fungal infections and in the pathogenesis of autoimmune diseases.

The IL-17 cytokine family consists of six cytokines (interleukins 17A to 17F) and five receptors (interleukins 17RA to 17RE). The interleukins 17A, 17F, and 17A/F heterodimer ligands share a common receptor subunit (interleukin-17RA) for signalling.

IL-17 is mainly produced by a subset of CD4 cells named Th-17 (T–helper 17) cells. It is mainly secreted by activated CD4+ and CD8+ T lymphocytes, while its receptor is found on many cell types.

What is the interleukin-17 pathway?

IL-17 has been classified as a pro-inflammatory cytokine because it induces the expression of mediators of inflammation involved in the proliferation, maturation, and chemotaxis of neutrophils.

  • IL-17A and IL-17F are protective against infections on the epithelial surfaces of the skin, lung, and oral cavity [1,2]
  • Signalling downstream of IL-17RA/RC elicits the expression of antimicrobial peptides (AMPs), including beta-defensins
  • IL-17 acts with IL-22 (produced mainly by T-helper 22 cells in humans) to induce expression of AMPs by keratinocytes [3]
  • IL-17A and IL-17F induce cytokines such as:
    • Interleukin (IL)-6
    • G-CSF (granulocyte colony-stimulating factor)
    • GM-CSF (granulocyte-macrophage colony-stimulating factor)
    • IL-1β (interleukin 1 beta)
    • TGF-β (transforming growth factor-beta)
    • TNF-α (tumour necrosis factor-alpha)
    • Chemokines, such as IL-8
    • Prostaglandins, such as PGE2
    • Matrix metalloproteinases (MMP) [3].

Overproduction of interleukins 17A, 17F, and 17A/F is associated with tissue damage and autoimmune diseases such as:

Skin diseases associated with interleukin-17

What is the protective role of interleukin-17 against infections?

The IL-17 family of cytokines play a role in the management of pathogens.

The same cytokines have also been reported to have functions outside the skin, at least trials involving mice. IL-17E has a protective role in CNS inflammation and participates in protective responses against parasites in the intestine [7–9].

Infections protected by IL-17

What skin diseases involve interleukin-17?

Skin diseases in which interleukin-17 is involved or is thought to be involved are as follows.


Psoriasis is a chronic inflammatory skin condition characterised by epidermal hyperplasia.

  • Elevated IL-17A and Th17-related cytokines, such as IL-22 and IL-23, are found in psoriatic plaques.
  • The IL-17A-blocking monoclonal antibodies secukinumab and ixekizumab and the IL-17RA-targeting antibody brodalumab result in marked improvement and sometimes complete clearance of psoriasis [10–12].
  • Several other molecules targeting the IL-17 family are in clinical development (eg, bimekizumab, which targets IL-17A and IL-17F), as are drugs targeting IL-23, which is upstream of IL-17, and signalling molecules, which are downstream [13,14].



The role of IL-17 is under investigation in various forms of dermatitis.

Skin cancer

IL-17 signalling has been associated with the development of skin cancer during chemical carcinogenesis in mouse models.

  • This pro-tumourigenic effect of IL-17 is thought to occur via the promotion of epithelial proliferation and the anti-apoptotic effect of the transcription factor STAT-3 (Signal Transducer and Activator of Transcription 3), which may be downstream of IL-17-induced genes such as IL-6.
  • IL-17A blockade may prove useful for controlling at least some cancers [16]. This is unproven in humans


Epithelial skin cancers

What are the future indications of the study of interleukin-17?

The proinflammatory properties of IL-17 are protective against infection. A good understanding of the different roles played by the IL-17 cytokines is necessary to design effective drugs relating to pathogenesis and mechanisms of inflammation.

  • Unrestrained IL-17 signalling is associated with immunopathology, autoimmune disease, and cancer progression.
  • IL-17 inhibitors are proving valuable in the control of inflammatory skin disease.
  • Analysis of the roles of individual components of the IL-17 pathway in infection and inflammation is ongoing.

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Related information



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