IL-36 in psoriasis
Highlights
► A new mouse model provides extensive support for a role of IL-36 in human plaque psoriasis. ► Further evidence comes from in vitro studies in multiple laboratories. ► Separately, reduction-in-function mutations in IL-36Ra have been implicated in generalized pustular psoriasis. ► Recent studies suggest activity of IL-36 in multiple additional organ systems, including lung, kidney and immune function.
Section snippets
The IL-36 family of cytokines
The cytokine IL-36 is a member of the IL-1 family of cytokines (see [1] for review). The family is named after its original members, IL-1α and IL-1β, although at the time that the biological activity of IL-1 was first characterized, it was not realized that it was encoded by two separate molecules. In the 2 decades since, 9 other family members have been discovered (see Figure 1). The term IL-36 actually refers to three separate molecules — IL-36α, IL-36β and IL-36γ — which as far as are known
IL-36 in psoriasis
Psoriasis is an immune-mediated inflammatory skin condition which occurs in approximately 2% of the European and North American population [4]. It is characterized by raised, red scaly skin lesions or plaques which histologically show acanthosis (increased thickness of the epidermis), hyperkeratosis (expansion of the cornified layer), parakeratosis (retention of nuclei in the cornified layer), an expanded capillary network in the superficial dermis, and an inflammatory infiltrate that includes
IL-36 in other tissues
While the majority of the studies on IL-36 have focused on the role of these cytokines in the skin, IL-36 ligands and the IL-36R are found in other tissues as well, in particular the lung but also in the joint, gut, kidney and brain. IL-36β mRNA is expressed in human synovial tissues, and synovial fibroblasts and articular chondrocytes produced IL-6 and IL-8 in response to IL-36β [17]. IL-36α expression is elevated in chronic kidney disease [18] and IL-36α and IL-36β can induce inflammatory
Conclusions
As reviewed in this article, IL-36 cytokines are strongly elevated in lesional skin from plaque psoriasis patients, and their continued action appears important in maintaining the lesional phenotype. Overexpression of IL-36α can also lead to psoriatic-like skin inflammation in mice. On the other hand, loss of IL-36Ra in humans results in susceptibility to generalized pustular psoriasis. It is interesting to contemplate the parallels to cryopyrinopathies such as Muckle–Wells syndrome,
Acknowledgement
The authors would like to thank Jason Douangpanya for generation of figures.
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