Effects of tumor necrosis factor-like ligand 1A (TL1A) on imiquimod-induced psoriasiform skin inflammation in mice

• Published in: Archives of Dermatological Research 2020-09, Vol.312 (7), p.481-490
• Main Authors: Li, Lin, Fu, Lixin, Zhou, Peimei, Lu, Yonghong, Zhang, Liwen, Wang, Wenju, Nie, Jianjun, Zhang, Dawei, Liu, Yan, Wu, Bo, Chen, Tao
• Format: Article
• Language: English
• Subjects: Animals; Antiviral drugs; Autoimmune diseases; CD11c antigen; CD3 antigen; Dermatology; Disease Models, Animal; Gene expression; Humans; Imiquimod; Imiquimod - administration & dosage; Imiquimod - toxicity; Inflammation; Injection; Interleukin 17; Lesions; Leukocytes (neutrophilic); Lymphocytes T; Male; Medicine; Medicine & Public Health; Mice; Monoclonal antibodies; Necrosis; Neutrophils; Original Paper; Phenotypes; Psoriasis; Psoriasis - chemically induced; Psoriasis - drug therapy; Psoriasis - immunology; Psoriasis - pathology; Rodents; Signal Transduction - drug effects; Signal Transduction - immunology; Skin; Skin - immunology; Skin - pathology; Tumor Necrosis Factor Ligand Superfamily Member 15 - administration & dosage; Tumor Necrosis Factor Ligand Superfamily Member 15 - antagonists & inhibitors; Tumor Necrosis Factor Ligand Superfamily Member 15 - metabolism; Tumor Necrosis Factor-alpha - metabolism; γ-Interferon
• ISSN: 0340-3696; 1432-069X
• DOI: 10.1007/s00403-019-02030-8

TL1A, as a master regulatory cytokine, plays a key role in the development of diverse T-cell-mediated inflammatory and autoimmune diseases. Our study is to further understand the roles of TL1A in the pathogenic mechanism of psoriasis and to find a possible new therapeutic strategy in the treatment of psoriasis. The direct effects of TL1A injection in mice skin and the therapeutic effects of TL1A blockade in imiquimod (IMQ)-induced psoriasis-like mouse model were researched in this study. First, we found that the expressions of TL1A in IMQ-treated lesions were significantly higher than Vaseline control group. And then, the results showed that TL1A injection exacerbated the psoriasiform phenotype on IMQ-treated skin (including clinical score, epidermal thickness changes, and Baker score) by increasing the number of T cells, neutrophils, and DCs, and upregulating the mRNA expression of IFN-γ and IL-17. However, anti-TL1A mAb can alleviate psoriasis-like lesions in clinical and effectively improved the histopathologic changes in IMQ-induced psoriasis-like mice after treatment. Moreover, anti-TL1A mAb also reduced the number of infiltrated CD3 + T cells, MPO +  neutrophils, and CD11c + DCs in psoriasis-like lesions, and obviously decreased the expression of IFN-γ and IL-17 in psoriasis-like lesions. Data suggested that TL1A might be involved in the pathogenesis of psoriasis, and targeting TL1A by anti-TL1A mAb might provide a solid foundation and novel therapeutic sight in the treatment of psoriasis.