Shi Feng, Gong Pixia, Huang Shan, Zhu Weidong, Shi Chenxi, Qi Chang, Lei Zhe, Ding Yayun
Department of Dermatology and Venereology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu, 215123, China.
NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Suzhou, Jiangsu, 215123, China.
Biol Direct. 2025 Sep 2;20(1):96. doi: 10.1186/s13062-025-00675-2.
Psoriasis is an immune-mediated chronic inflammatory condition characterized by significant neutrophil infiltration in the skin. Given that the spleen is the largest peripheral immune organ in the body, it is important to investigate whether it has any impact on skin inflammation in psoriasis.
To investigate this mechanism, a psoriatic mouse model was established by IMQ application. Flow cytometry and immunohistochemistry analyses were performed to determine the percentage of various immune cells in the spleen. The role of neutrophils was specifically assessed using the anti-Gr-1 antibody. Splenic granulopoiesis was evaluated using EdU labeling. To understand the spleen's role in skin inflammation, splenectomy was performed on the experimental mice. IL-6 levels were measured by ELISA, and P-STAT3 in neutrophils was detected via immunofluorescence. Further examination of IL-6's effects on neutrophil formation involved treating mice with IL-6 antibody. The severity of psoriasis was evaluated through histological staining and PASI scoring.
Our study revealed that the spleens of psoriatic mice were enlarged compared to those of vehicle mice. Among immune cell populations, neutrophils showed the most significant changes, with marked increases in both spleen and skin of psoriatic mice and patients, contributing to disease progression. Post-splenectomy, neutrophil infiltration in the skin was reduced by approximately 60% in psoriatic mice. This indicates that the neutrophils in the skin were primarily derived from the spleen. Additionally, the spleen showed a notable capacity for granulopoiesis with elevated neutrophils. Moreover, we found elevated IL-6 levels in the skin, blood, and spleen in the model, which was decreased after splenectomy. Treatment with an IL-6 antibody reduced neutrophil formation in both the spleen and skin, which alleviated skin inflammation in psoriatic mice. Additionally, P-STAT3 signaling was decreased following IL-6 antibody treatment. The neutrophil infiltration in spleen and skin was decreased after injection with the inhibitor of P-STAT3, which also alleviated the inflammation of psoriatic model. Thus, IL-6 served as the dominant regulator of spleen granulopoiesis, a process potentially mediated by P-STAT3 signaling.
The spleen plays a crucial role in the immune microenvironment of psoriasis as a major site of granulopoiesis, influencing neutrophil infiltration in the skin of psoriatic mice. Additionally, IL-6 is a key regulator of neutrophil formation in the spleen of psoriatic mice, likely through P-STAT3-dependent mechanisms.
银屑病是一种免疫介导的慢性炎症性疾病，其特征是皮肤中有大量中性粒细胞浸润。鉴于脾脏是人体最大的外周免疫器官，研究其是否对银屑病的皮肤炎症有任何影响很重要。
为了研究这一机制，通过应用咪喹莫特建立了银屑病小鼠模型。进行流式细胞术和免疫组织化学分析以确定脾脏中各种免疫细胞的百分比。使用抗Gr-1抗体特异性评估中性粒细胞的作用。使用EdU标记评估脾脏粒细胞生成。为了了解脾脏在皮肤炎症中的作用，对实验小鼠进行了脾切除术。通过ELISA测量IL-6水平，通过免疫荧光检测中性粒细胞中的P-STAT3。进一步研究IL-6对中性粒细胞形成的影响涉及用IL-6抗体治疗小鼠。通过组织学染色和PASI评分评估银屑病的严重程度。
我们的研究表明，与载体小鼠相比，银屑病小鼠的脾脏肿大。在免疫细胞群体中，中性粒细胞变化最为显著，银屑病小鼠和患者的脾脏和皮肤中均显著增加，促进了疾病进展。脾切除术后，银屑病小鼠皮肤中的中性粒细胞浸润减少了约60%。这表明皮肤中的中性粒细胞主要来源于脾脏。此外，脾脏显示出显著的粒细胞生成能力，中性粒细胞增多。此外，我们发现模型中皮肤、血液和脾脏中的IL-6水平升高，脾切除术后降低。用IL-6抗体治疗可减少脾脏和皮肤中的中性粒细胞形成，减轻银屑病小鼠的皮肤炎症。此外，IL-6抗体治疗后P-STAT3信号降低。注射P-STAT3抑制剂后，脾脏和皮肤中的中性粒细胞浸润减少，这也减轻了银屑病模型的炎症。因此，IL-6作为脾脏粒细胞生成的主要调节因子，这一过程可能由P-STAT3信号介导。
脾脏作为粒细胞生成的主要部位，在银屑病的免疫微环境中起关键作用，影响银屑病小鼠皮肤中的中性粒细胞浸润。此外，IL-6可能通过P-STAT3依赖性机制，是银屑病小鼠脾脏中中性粒细胞形成的关键调节因子。
Zotero 插件