###### Abstract  
The interleukin (IL)-1 family of cytokines is composed of 11 members, including the most recently discovered IL-36\(\alpha\), \(\beta\), \(\gamma\), IL-37, and IL-38. Similar to IL-1, IL-36 cytokines are initiators and amplifiers of inflammation, whereas both IL-37 and IL-38 display anti-inflammatory activities. A few studies have outlined the role played by these cytokines in several inflammatory diseases. For instance, IL-36 agonists seem to be relevant for the pathogenesis of skin psoriasis whereas, despite being expressed within the synovial tissue, their silencing or overexpression do not critically influence the course of arthritis in mice. In this review, we will focus on the state of the art of the molecular features and biological roles of IL-36, IL-37, and IL-38 in representative skin- and joint-related inflammatory diseases, namely psoriasis, rheumatoid arthritis, and psoriatic arthritis. We will then offer an overview of the therapeutic potential of targeting the IL-36 axis in these diseases, either by blocking the proinflammatory agonists or enhancing the physiologic inhibitory feedback on the inflammation mediated by the antagonists IL-37 and IL-38.  
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enthesitis, or peripheral arthritis [3]. The diagnosis of PsA is sometimes laborious because of the huge variety of the presenting manifestations. It relies on the classification criteria published by the CASPAR (CIASification criteria for Psoriatic ARthritis) group, which include (i) evidence of psoriasis, (ii) psoriatic nail dystrophy, (iii) negative tests for RA, (iv) dactylitis, and (v) radiographic evidence of juxta-articular new bone formation [4]. Although psoriasis and PsA share common features such as genetic susceptibility, comorbidities, or certain pathogenic immunologic pathways, several important tissue-specific differences exist, as highlighted in a recent publication from our group [5]. RA is the most common chronic autoimmune joint disease, impacting \(\sim\)0.3% of the population worldwide [6]. It is characterized by the inflammatory hyperplasia of the synovial membrane of diarthrodial joints and the subsequent cartilage destruction and bone erosions. The progressive damage of the articular structures causes disabilities and impairs patients' quality of life.  
The introduction of biologics into the therapeutic arsenal enabled a notable improvement of the clinical outcome of patients affected by skin psoriasis as well as psoriatic and rheumatoid arthritis. However, the efficacy of the currently available agents varies from patient to patient, and a still considerably high number of subjects fail to respond. Since the suboptimal response and the lack of prognostic predictors constitute significant health and economic burden, further research directed towards identifying novel therapeutic targets for the treatment of psoriasis/PsA and RA is needed.  
Interestingly, the specific targeting of IL-36 by blocking its receptor (IL-36R) has already shown compelling anti-inflammatory effects in skin psoriasis; however, exploiting the properties of the antagonists IL-37 and IL-38 may represent an even more powerful weapon to inhibit IL-1-, Toll-Like Receptor (TLR)-, and IL-36-driven inflammation. Here, we will provide a comprehensive and updated description of the molecular and biologic features of the IL-36, IL-37, and IL-38 agonists and antagonists, particularly in the context of psoriasis, PsA and RA. At the same time, we will explore the therapeutic potential of targeting the IL-36 axis to control skin and joint inflammation.