Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, Shanghai, China.
Division of Infectious Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Front Immunol. 2022 Dec 15;13:1076594. doi: 10.3389/fimmu.2022.1076594. eCollection 2022.
Tetraspanin proteins are closely related to the functional changes of B cells, including antigen presentation, production of cytokines, and transduction. We aim to explore the potential role of Tetraspanin 1 (TSPAN1) in the biological activities of B cells in AIH.
Herein, this study found that numbers of cells expressing TSPAN1 were significantly increased in AIH patients compared to PBC, chronic hepatitis B, and healthy control (P < 0.0001). Moreover, there was a positive correlation between numbers of TSPAN1+ cells and AIH disease severity (P < 0.0001). Immunofluorescence staining further confirmed that TSPAN1 was primarily expressed on CD19+ B cells. Flow-cytometric analysis showed that TSPAN1+ B cells secreted more inflammatory cytokines and expressed higher level of CD86 than TSPAN1- B cells. Furthermore, compared with TSAPN1- cells, the expression of CXCR3 on TSPAN1+ cells was also higher. Meanwhile, CXCL10, the ligand of CXCR3, was significantly elevated in the liver of AIH (P < 0.01) and had positive correlation with the quantities of TSPAN1 (P < 0.05). Interestingly, the numbers of TSPAN1+ B cells were decreased in AIH patients after immunosuppressive therapy.
TSPAN1 B cells in the liver may promote the progression of AIH secreting cytokines and presenting antigens. The chemotactic movement of TSPAN1 B cells toward the liver of AIH was possibly due to CXCR3 - CXCL10 interaction.
四跨膜蛋白与 B 细胞的功能变化密切相关，包括抗原呈递、细胞因子产生和转导。我们旨在探讨四跨膜蛋白 1（TSPAN1）在 AIH 中 B 细胞生物学活性中的潜在作用。
本研究发现，与 PBC、慢性乙型肝炎和健康对照相比，AIH 患者表达 TSPAN1 的细胞数量显著增加（P<0.0001）。此外，TSPAN1+细胞数量与 AIH 疾病严重程度呈正相关（P<0.0001）。免疫荧光染色进一步证实 TSPAN1 主要表达于 CD19+B 细胞上。流式细胞术分析显示，TSPAN1+B 细胞分泌更多的炎症细胞因子，表达更高水平的 CD86 比 TSPAN1-B 细胞。此外，与 TSPAN1-细胞相比，TSPAN1+细胞上 CXCR3 的表达也更高。同时，CXCL10，CXCR3 的配体，在 AIH 肝组织中显著升高（P<0.01），并与 TSPAN1 的数量呈正相关（P<0.05）。有趣的是，免疫抑制治疗后 AIH 患者 TSPAN1+B 细胞数量减少。
肝脏中的 TSPAN1+B 细胞可能通过分泌细胞因子和呈递抗原促进 AIH 的进展。TSPAN1+B 细胞向 AIH 肝脏的趋化运动可能是由于 CXCR3-CXCL10 相互作用所致。
