Background

Psoriasis is a skin inflammatory disease affecting 3% of the population (Girolomoni et al., 2017; Zhong et al., 2018). Psoriasis etiology is still unclear, but a strong association with human leukocyte antigens (HLA) was documented (Knight et al., 2012; Tsoi et al., 2012). Environmental factors like sex, stress, and smoking affect the clinical manifestations of psoriasis (Fry and Baker, 2007). Keratinocyte hyperproliferation, increased blood vessel formation, and infiltration of immune cells are common in psoriasis skin (Van der Fits et al., 2009). Innate and adaptive immune responses are indispensable for disease development (Villanova et al., 2014). Proinflammatory cytokines and the immune cells secreting them activate the effector cells present in the skin. For example, T cell–derived cytokines like IL-17A and IL-17F activate keratinocytes, which produce anti-microbial peptides and more cytokines and chemokines. These inflammatory factors shape psoriasis skin inflammation (Ando et al., 2015).

Mannan is present in nearly all fungi species. Saccharomyces cerevisiae and Candida albicans mannans are pathogenic factors in psoriasis (Picciani et al., 2013). An intraperitoneal injection of mannan extracted from Saccharomyces cerevisiae cell wall was shown to induce psoriatic arthritis and psoriasis symptoms in reactive oxygen species (ROS)-deficient, Ncf1-gene-mutated mice that are available only in specific labs (Khmaladze et al., 2014). On the other hand, an epicutaneous application of imiquimod (IMQ) for 5–7 days leads to the development of an acute psoriasis phenotype. However, the disease developed in IMQ-induced psoriasis is often accompanied by severe weight loss in BALB/c mice (Swindell et al., 2017). Herein, we describe an induction protocol for plaque psoriasis-like inflammation in an inbred mouse strain (BALB/c) by epicutaneous application of mannan (Figure 1). A local (epicutaneous) instead of the intraperitoneal application of mannan could mimic a more natural way of skin exposure to environmental triggers for skin disease induction. Induced skin inflammation resembles human plaque psoriasis. Redness covered with white scales and skin thickness in the lesion area in mannan-exposed skin is more straightforward, making this model simpler for visually observing most manifestations of the disease.

Figure 1. Clinical scoring for psoriasis inflammation. A representative psoriasis inflammation scoring method is given. PASI scores for the above skin conditions are as follows: redness: 4; scales: 3; thickness: 3. Each group contains 10 mice. BALB/cfemale mice were used for experiments. Left column pictures were reproduced from Figure 1A of the published paper (Wu et al., 2023).

Moreover, the proliferation of keratinocytes and innate immune cells, the infiltration of T lymphocytes in the skin, and an increased expression of proinflammatory cytokines were induced after epicutaneous mannan application (Wu et al., 2023). The activation of TLR7 and TLR8, mainly expressed in the immune cells, mediates the effects of IMQ (Bong et al., 2002). In contrast, mannan is a ligand for mannose receptors and is the primary trigger of IL-17 pathways in the host (Jiang et al., 2017). In addition, a higher-level expression of TLR2, TLR4, CD206, Dectin-2, Mincle, and DC-SIGN receptors was found in mannan-induced skin inflammation (MISI) (Wu et al., 2023). Thus, this disease model differs from IMQ-induced psoriasis-like inflammation, mainly in terms of the health status of the animals. Unlike the IMQ model, the body weight loss in MISI is negligible.

Furthermore, mannan had a shorter exposure time (3 days) to induce the disease than IMQ (5–7 days), demonstrating more cost-effective and convenient features. A response to dexamethasone in MISI has shown its usefulness in testing and validating various anti-psoriatic drugs for future treatments in psoriasis patients. Many autoimmune diseases show sexual dimorphism during disease development, and this plaque psoriasis-like skin inflammation induced by mannan also showed strong female preponderance, demonstrating its use in exploring sex-dependent mechanisms (Wu et al., 2022). Although mannan-induced skin inflammation results in acute and relapsing disease symptoms after repeated exposure, like other induced acute psoriasis mouse models, this model can also not completely mimic the relapsing and chronic characteristic features of human plaque psoriasis.