- IL-36 cytokines are composed of three agonists, namely IL-36α, IL-36β, and IL-36γ, and a natural antagonist, IL-36Ra (Sims and Smith, 2010). IL-36 cytokines are abundantly expressed by the skin and other epithelial tissues, whereas the IL-36 receptor (IL-36R) is expressed by skin and immune cells, including dendritic cells (DCs) (Gabay and Towne, 2015; Vigne et al., 2011). Earlier studies have demonstrated that IL-36 cytokines play important roles in the development of psoriasiform inflammation by enhancing the function of T helper type 17 cytokines (Carrier et al., 2011; Tortola et al., 2012).
- Intradermal injection of IL-23 and topical application of imiquimod (IMQ) are two widely adopted murine models of psoriasis. Both models result in psoriasiform dermatitis (PsD) in mice that resembles human psoriasis (van der Fits et al., 2009; Zheng et al., 2007). CCR6 is important for epidermal trafficking of IL-17/22–producing cells (Mabuchi et al., 2013) and is required for the development of PsD in the IL-23 injection model since CCR6-deficient knockout (CCR6KO) mice fail to show significant dermal inflammation (Hedrick et al., 2009).
- Keratinocytes are key players in chronic inflammatory skin diseases. A20 regulates NF-κB–dependent expression of proinflammatory genes and cell death, but the impact of its expression in keratinocytes on systemic inflammation and skin disorders has not been determined. Comparative transcriptomic analysis of microdissected epidermis showed that A20 is down-regulated in involved epidermis, but not in dermis, of psoriasis and atopic dermatitis patients, suggesting that loss of A20 expression in keratinocytes increases the vulnerability for psoriasis/atopic dermatitis induction.
- This study revealed the modulatory role of transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) cation channels in the Aldara-induced (5% imiquimod) murine psoriasis model using selective antagonists and genetically altered animals. We have also developed a refined localized model to enable internal controls and reduce systemic effects. Skin pathology was quantified by measuring skin thickness, scaling, blood flow, and analyzing dermal cellular infiltrate, whereas nocifensive behaviors were also observed.
- Psoriasis vulgaris is a common, inflammatory skin disease affecting approximately 3% of the population in the United States. The etiology of psoriasis and its associated comorbidities are complex and the result of complicated interactions between the skin, immune system, disease-associated susceptibility loci, and multiple environmental triggers. The modeling of human disease in vivo through the use of murine models represents a powerful, indispensable tool for investigating the immune and genetic mechanisms contributing to a clinical disease phenotype.
- The neuropeptide galanin is distributed in the central and peripheral nervous systems and in non-neuronal peripheral organs, including the skin. Galanin acts via three G protein-coupled receptors which, except galanin receptor 1, are expressed in various skin structures. The galanin system has been associated with inflammatory processes of the skin and of several other organs. Psoriasis is an inflammatory skin disease with increased neovascularization, keratinocyte hyperproliferation, a proinflammatory cytokine milieu, and immune cell infiltration.
- IL-6 inhibition has been unsuccessful in treating psoriasis, despite high levels of tissue and serum IL-6 in patients. In addition, de novo psoriasis onset has been reported after IL-6 blockade in patients with rheumatoid arthritis. To explore mechanisms underlying these clinical observations, we backcrossed an established psoriasiform mouse model (IL-17C+ mice) with IL-6-deficient mice (IL-17C+KO) and examined the cutaneous phenotype. IL-17C+KO mice initially exhibited decreased skin inflammation; however, this decrease was transient and reversed rapidly, concomitant with increases in skin Tnf, Il36α/β/γ, Il24, Epgn, and S100a8/a9 to levels higher than those found in IL-17C+ mice.