Wenjuan Chen1, Yu Gong1, Xilin Zhang2, Yunlei Tong1, Xiuxiu Wang3, Chengwen Fei1, Hui Xu1, Qian Yu1, Yao Wang1, Yuling Shi4. 1. Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. 2. Department of Dermatology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. 3. Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China. 4. Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: shiyuling1973@tongji.edu.cn.
Abstract
BACKGROUND: Psoriasis is a high-incident T-cell-mediated autoimmune disease mainly affecting the skin. Interleukin (IL)-27 is a novel member of the IL-6/IL-12 cytokine family, which plays a versatile role in the differentiation and function of distinct T cell subsets. Previous studies uncovered that IL-27 promoted the onset of psoriasis through enhancing the differentiation of T helper (Th) 1 cells. However, the role of IL-27 in other psoriasis-related Th lineages, especially Th17 cells, remains elusive. OBJECTS: The study aimed to investigate the role of IL-27 in the progression of psoriasis and its underlying mechanisms, particularly its influence on Th1 and Th17. METHODS: IL-27 and IL-27 receptor α (IL-27Rα) expressions in normal and lesional skin were determined by immunohistochemistry and western blot analysis. Serum levels of IL-27 and IL-10 were measured by ELISA. Expression levels of IL-27 and IL-27 receptor (IL-27R) mRNA in the skin tissue and peripheral blood mononuclear cells (PBMC) were assessed by quantitative polymerase chain reaction (PCR) analysis. To explore the function of IL-27 in vivo, we used imiquimod (IMQ)-induced psoriasis mouse model. We treated mice with IL-27 or its antagonist, evaluated disease severity and detected the cytokine secretion from splenic CD4+ T cells by flow cytometric analysis and the expression levels of IL-17 and IFN-γ in serum and skin lesion. RESULTS: The expression levels of IL-27 and IL-27Rα were significantly reduced in the moderate-to-severe psoriatic lesions, along with a consistent decrease in serum IL-27 levels, compared with those of healthy control subjects. Moreover, subcutaneous administration of IL-27 recombinant protein lessened severity of IMQ-induced psoriasis-like cutaneous lesions, whereas IL-27p28 antagonist exaggerated the disease severity. Further analysis revealed that IL-27 significantly repressed IL-17 secretion from CD4+ T lymphocytes. Also administration of IL-27 decreased IL-17A level while IL-27p28 antagonist increased IL-17A level in serum and psoriasis-like lesion in the IMQ-treated mice. CONCLUSION: Our results suggest that IL-27 might predominantly play a protective role in the pathogenesis of psoriasis through abrogating Th17 differentiation. The potential therapeutic benefit of harnessing IL-27 in treating psoriasis awaits future investigation.
BACKGROUND:Psoriasis is a high-incident T-cell-mediated autoimmune disease mainly affecting the skin. Interleukin (IL)-27 is a novel member of the IL-6/IL-12 cytokine family, which plays a versatile role in the differentiation and function of distinct T cell subsets. Previous studies uncovered that IL-27 promoted the onset of psoriasis through enhancing the differentiation of T helper (Th) 1 cells. However, the role of IL-27 in other psoriasis-related Th lineages, especially Th17 cells, remains elusive. OBJECTS: The study aimed to investigate the role of IL-27 in the progression of psoriasis and its underlying mechanisms, particularly its influence on Th1 and Th17. METHODS:IL-27 and IL-27 receptor α (IL-27Rα) expressions in normal and lesional skin were determined by immunohistochemistry and western blot analysis. Serum levels of IL-27 and IL-10 were measured by ELISA. Expression levels of IL-27 and IL-27 receptor (IL-27R) mRNA in the skin tissue and peripheral blood mononuclear cells (PBMC) were assessed by quantitative polymerase chain reaction (PCR) analysis. To explore the function of IL-27 in vivo, we used imiquimod (IMQ)-induced psoriasismouse model. We treated mice with IL-27 or its antagonist, evaluated disease severity and detected the cytokine secretion from splenic CD4+ T cells by flow cytometric analysis and the expression levels of IL-17 and IFN-γ in serum and skin lesion. RESULTS: The expression levels of IL-27 and IL-27Rα were significantly reduced in the moderate-to-severe psoriatic lesions, along with a consistent decrease in serum IL-27 levels, compared with those of healthy control subjects. Moreover, subcutaneous administration of IL-27 recombinant protein lessened severity of IMQ-induced psoriasis-like cutaneous lesions, whereas IL-27p28 antagonist exaggerated the disease severity. Further analysis revealed that IL-27 significantly repressed IL-17 secretion from CD4+ T lymphocytes. Also administration of IL-27 decreased IL-17A level while IL-27p28 antagonist increased IL-17A level in serum and psoriasis-like lesion in the IMQ-treated mice. CONCLUSION: Our results suggest that IL-27 might predominantly play a protective role in the pathogenesis of psoriasis through abrogating Th17 differentiation. The potential therapeutic benefit of harnessing IL-27 in treating psoriasis awaits future investigation.
Authors: Tamara Moreno-Sosa; María Belén Sánchez; Elisa Olivia Pietrobon; Juan Manuel Fernandez-Muñoz; Felipe Carlos Martín Zoppino; Flavia Judith Neira; María José Germanó; Diego Esteban Cargnelutti; Alicia Carolina Innocenti; Graciela Alma Jahn; Susana Ruth Valdez; Juan Pablo Mackern-Oberti Journal: Front Immunol Date: 2021-04-29 Impact factor: 7.561