Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA.
Aliment Pharmacol Ther. 2014 Aug;40(3):261-79. doi: 10.1111/apt.12825. Epub 2014 Jun 2.
Chemokines contribute to the pathogenesis of autoimmune hepatitis by directing the migration and positioning of inflammatory and immune cells within the liver.
Describe the liver-infiltrating effector cell populations in autoimmune hepatitis, indicate the chemokines that influence their migration, describe the role of chemokines in hepatic fibrosis and identify chemokine-directed treatment opportunities.
Studies cited in Pub Med from 1972 to 2014 for autoimmune hepatitis, chemokines in liver disease, pathogenesis of autoimmune hepatitis and chemokine therapy were selected.
T helper type 17 lymphocytes expressing CXCR3 and CCR6 are attracted to the liver by the secretion of CXCL9, CXCL10 and CXCL11. These cells recruit pro-inflammatory T helper type 1 lymphocytes expressing CXCR3 and CCR5 by secreting CXCL10. Resident natural killer T cells expressing CXCR6 migrate in response to the local secretion of CXCL16, and they modulate the inflammatory response. T helper type 2 lymphocytes expressing CCR4 are attracted by CCL17 and CCL22, and they dampen the expansion of pro-inflammatory cells. Regulatory T cells expressing CXCR3 are attracted by the secretion of CXCL9, and they help dampen the pro-inflammatory responses. CCL2, CCL3, CCL5, CXCL4, CXCL10 and CXCL16 promote fibrosis by activating or attracting hepatic stellate cells, and CX3CL1 may prevent fibrosis by affecting the apoptosis of monocytes.
Chemokines are requisites for mobilising, directing and positioning the effector cells in immune-mediated liver disease. They are feasible therapeutic targets in autoimmune hepatitis, and the evaluation of monoclonal antibodies that neutralise the pro-inflammatory ligands or designer peptides that block receptor activity are investigational opportunities.
趋化因子通过指导炎症和免疫细胞在肝脏内的迁移和定位，促进自身免疫性肝炎的发病机制。
描述自身免疫性肝炎中的肝浸润效应细胞群体，指出影响其迁移的趋化因子，描述趋化因子在肝纤维化中的作用，并确定趋化因子靶向治疗的机会。
从 1972 年至 2014 年，在 Pub Med 上选择了与自身免疫性肝炎、肝脏疾病中的趋化因子、自身免疫性肝炎发病机制和趋化因子治疗相关的研究。
表达 CXCR3 和 CCR6 的 Th17 淋巴细胞通过分泌 CXCL9、CXCL10 和 CXCL11 被吸引到肝脏。这些细胞通过分泌 CXCL10 招募表达 CXCR3 和 CCR5 的促炎 Th1 淋巴细胞。表达 CXCR6 的固有自然杀伤 T 细胞对局部分泌的 CXCL16 有迁移反应，并调节炎症反应。表达 CCR4 的 Th2 淋巴细胞被 CCL17 和 CCL22 吸引，并抑制促炎细胞的扩增。表达 CXCR3 的调节性 T 细胞被 CXCL9 的分泌所吸引，并有助于抑制促炎反应。CCL2、CCL3、CCL5、CXCL4、CXCL10 和 CXCL16 通过激活或吸引肝星状细胞促进纤维化，而 CX3CL1 可能通过影响单核细胞的凋亡来预防纤维化。
趋化因子是动员、指导和定位免疫介导的肝脏疾病效应细胞的必要条件。它们是自身免疫性肝炎可行的治疗靶点，评估中和促炎配体的单克隆抗体或阻断受体活性的设计肽是研究机会。
