Abstract
Psoriasis, the most common skin inflammatory disease, is characterized by massive keratinocyte proliferation and immune cell infiltration into epidermis. L-Theanine (L-THE), a nonproteinogenic amino acid derived from green tea (Camellia sinensis), has been proved to possess the properties of anti-inflammatory, antidepressants and neuroprotective. However, whether L-THE has a therapeutic effect on psoriasis is still unknown. In this study, we found that the epidermal thickness and inflammatory response were significantly reduced in Imiquimod (IMQ)-induced psoriasis mice by applying with L-THE on mice skin. The expression of proliferation and inflammation associated genes such as keratin 17, IL-23 and CXCL1-3 was also downregulated by L-THE. Furthermore, L-THE inhibited the production of IL-23 in dendritic cells (DCs) after IMQ treatment, and decreased the levels of chemokines in keratinocytes treated with IL-17A by downregulating the expression of IL-17RA. RNA-seq and KEGG analysis revealed that L-THE significantly regulated the expression of IL-17A and NF-κB signaling pathway-associated genes. Metabolomics analysis displayed that L-THE promoted propanoate metabolism which has been reported to inhibit the activity of TH17 cells. Therefore, our results demonstrated that L-THE significantly decreases the levels of IL-23 and chemokines, and attenuates IMQ-induced psoriasis like skin inflammation by inhibiting the activation of NF‐κB and IL-17A signaling pathways, and promoting the propanoate metabolism. Our findings suggest that topical applied L-THE can be used as a topical drug candidate for the treatment of psoriasis or as an adjuvant treatment of ustekinumab or secukinumab to prevent the relapse of psoriasis.
Highlights
Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders, affecting about 2–3% of the population worldwide (Gonzalez-Cantero et al, 2021)
These discoveries have promoted the development of biologics for psoriasis, such as Ustekinumab targeting interleukin 23 (IL-23), Secukinumab targeting IL-17 which have been approved by the US Food and Drug Administration to treat psoriasis, and result in dramatic improvements in approximately 80–90% of psoriasis patients (Campa et al, 2016; Boutet et al, 2018; Ghoreschi et al, 2021)
We found that the swelling, epidermal acanthosis, skin inflammation, and proliferation of keratinocytes were extenuated after L-THE treatment in the back skin after treatment with IMQ cream for 5 days (Figure 1E)
Summary
Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders, affecting about 2–3% of the population worldwide (Gonzalez-Cantero et al, 2021). A large number of studies have shown that the deregulated production of IL-23 secreted by DCs can initiate the progression of psoriasis (Lillis et al, 2010; Kagami, 2011). These discoveries have promoted the development of biologics for psoriasis, such as Ustekinumab targeting IL-23, Secukinumab targeting IL-17 which have been approved by the US Food and Drug Administration to treat psoriasis, and result in dramatic improvements in approximately 80–90% of psoriasis patients (Campa et al, 2016; Boutet et al, 2018; Ghoreschi et al, 2021). There is always a lack of effective measures to prevent the recurrence of psoriasis
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