Montano-Loza Aldo J, Czaja Albert J
Division of Gastroenterology and Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada.
Dig Dis Sci. 2015 Jun;60(6):1528-42. doi: 10.1007/s10620-014-3473-z. Epub 2014 Dec 9.
Autoimmune hepatitis is associated with interactive cell populations of the innate and adaptive immune systems, and these populations are amenable to therapeutic manipulation. The goals of this review are to describe the key cell populations implicated in autoimmune hepatitis and to identify investigational opportunities to develop cell-directed therapies for this disease. Studies cited in PubMed from 1972 to 2014 for autoimmune hepatitis, innate and adaptive immune systems, and therapeutic interventions were examined. Dendritic cells can promote immune tolerance to self-antigens, present neo-antigens that enhance the immune response, and expand the regulatory T cell population. Natural killer cells can secrete pro-inflammatory and anti-inflammatory cytokines and modulate the activity of dendritic cells and antigen-specific T lymphocytes. T helper 2 lymphocytes can inhibit the cytotoxic activities of T helper 1 lymphocytes and limit the expansion of T helper 17 lymphocytes. T helper 17 lymphocytes can promote inflammatory activity, and they can also up-regulate genes that protect against oxidative stress and hepatocyte apoptosis. Natural killer T cells can expand the regulatory T cell population; gamma delta lymphocytes can secrete interleukin-10, stimulate hepatic regeneration, and induce the apoptosis of hepatic stellate cells; and antigen-specific regulatory T cells can dampen immune cell proliferation and function. Pharmacological agents, neutralizing antibodies, and especially the adoptive transfer of antigen-specific regulatory T cells that have been freshly generated ex vivo are evolving as management strategies. The cells within the innate and adaptive immune systems are key contributors to the occurrence of autoimmune hepatitis, and they are attractive therapeutic targets.
自身免疫性肝炎与先天性和适应性免疫系统的相互作用细胞群体相关，并且这些群体适合进行治疗性调控。本综述的目的是描述与自身免疫性肝炎相关的关键细胞群体，并确定开发针对该疾病的细胞定向疗法的研究机会。检索了1972年至2014年PubMed中关于自身免疫性肝炎、先天性和适应性免疫系统以及治疗干预的研究。树突状细胞可促进对自身抗原的免疫耐受，呈递增强免疫反应的新抗原，并扩大调节性T细胞群体。自然杀伤细胞可分泌促炎和抗炎细胞因子，并调节树突状细胞和抗原特异性T淋巴细胞的活性。辅助性T细胞2淋巴细胞可抑制辅助性T细胞1淋巴细胞的细胞毒性活性，并限制辅助性T细胞17淋巴细胞的扩增。辅助性T细胞17淋巴细胞可促进炎症活动，还可上调抵御氧化应激和肝细胞凋亡的基因。自然杀伤T细胞可扩大调节性T细胞群体；γδ淋巴细胞可分泌白细胞介素-10，刺激肝再生，并诱导肝星状细胞凋亡；抗原特异性调节性T细胞可抑制免疫细胞的增殖和功能。药理学药物、中和抗体，尤其是体外新鲜生成的抗原特异性调节性T细胞的过继转移正逐渐成为治疗策略。先天性和适应性免疫系统中的细胞是自身免疫性肝炎发生的关键因素，也是有吸引力的治疗靶点。
