Abstract
Interleukin-36 (IL-36) comprises to a cytokine family consisting of four isoforms IL-36α, IL-36β, IL-36γ, and IL-36 receptor antagonist (IL-36 Ra). These IL-36 cytokines, in turn, belong to the IL-1 superfamily. The IL-36 receptor (IL-1R6) is functional as a heterodimer formed of IL-1R6 and IL-1 receptor accessory protein (IL-1RAcP). IL-36α, IL-36β, and IL-36γ are regarded as pro-inflammatory ligands and IL-36 Ra as well as IL-38 as anti-inflammatory ligands of IL-1R6. IL-36 cytokines are mainly expressed on the barrier sites of the body e.g., bronchial, intestinal, and dermal epithelium. One of their most important biological functions is the bridging of innate and adaptive immune responses. A disturbed balance between pro-inflammatory and anti-inflammatory branches easily leads to inflammation of the corresponding tissue. The most prominent example for an altered IL-36 expression is the spectrum of psoriasis. In addition to inflammatory dermatoses, IL-36 also seems to play a role in infectious dermatoses. Microbial triggers, especially Staphylococcus aureus infection, increase the production of pro-inflammatory IL-36 cytokines and initiate/promote the inflammation of skin lesions. Due to the discovery of IL-36 as an important immune mediator, it has already been possible to develop important diagnostic tools for dermatitis. Not only in the field of inflammatory skin diseases, but also in pulmonary and intestinal inflammation, there is evidence that IL-36 cytokines might have diagnostic and/or therapeutic relevance.
Highlights
Interleukin-36 (IL-36) is a member of the IL-1 superfamily discovered about 20 years ago [1,2,3]
It was shown in a murine psoriasis model that the vitamin D3 derivative calcipotriol inhibits the expression of IL-36α and IL-36γ in keratinocytes via their vitamin D receptor, which in turn prevents the infiltration of neutrophils [92] and saves skin from inflammation
IL-36 cytokines regulate themselves by its natural antagonists, IL-36 receptor antagonist (Ra) and IL-38, which prevents from hyper inflammation of the corresponding tissue in a healthy state
Summary
Interleukin-36 (IL-36) is a member of the IL-1 superfamily discovered about 20 years ago [1,2,3]. The four existing isoforms have been renamed several times [4]. They were formerly known as IL-1F6, IL-1F8, IL-1F9, and IL-1F5. Since their functions were revealed about one decade ago, they were assigned as IL-36α, IL-36β, IL-36γ, and IL-36 receptor antagonist (Ra) [4, 5]. The expression of IL-36 cytokines and IL-36 receptor (IL-1R6) has been described in many different tissues (Table 1). The IL-36 isoforms IL-36α, IL-36β, IL-36γ, and IL-36 receptor antagonist (IL-36 Ra) are predominantly produced in the skin by keratinocytes [20]. The isoforms IL-36α and IL-36γ are expressed in the respiratory tract [21] and IL-36β as TABLE 1 | Overview about IL-36 isoforms
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