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

Abstract

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.

• Authors: Lin Li, Lixin Fu, Peimei Zhou, Yonghong Lu, Liwen Zhang, Wenju Wang, Jianjun Nie, Dawei Zhang, Yan Liu, Bo Wu, Tao Chen
• Journal: Archives of dermatological research (Arch Dermatol Res) Vol. 312 Issue 7 Pg. 481-490 (Sep 2020) ISSN: 1432-069X [Electronic] Germany
• PMID: 31953572 (Publication Type: Journal Article)

Chemical References

• Tnf protein, mouse
• Tnfsf15 protein, mouse
• Tumor Necrosis Factor Ligand Superfamily Member 15
• Tumor Necrosis Factor-alpha
• Imiquimod

Topics

• Animals
• Disease Models, Animal
• Humans
• Imiquimod (administration & dosage, toxicity)
• Male
• Mice
• Psoriasis (chemically induced, drug therapy, immunology, pathology)
• Signal Transduction (drug effects, immunology)
• Skin (immunology, pathology)
• Tumor Necrosis Factor Ligand Superfamily Member 15 (administration & dosage, antagonists & inhibitors, metabolism)
• Tumor Necrosis Factor-alpha (metabolism)