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肝白血病因子指导组织内炎性记忆CD4⁺ T细胞的存在

Masahiro Kiuchi¹, Masahiro Nemoto¹, Hiroyuki Yagyu^1,2

¹Department of Immunology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.

Science (New York, N.Y.)

|December 11, 2025

概括

肝白血病因子 (HLF) 被确定为CD4+组织内存T (T_RM) 细胞的关键调节剂. 这一发现揭示了HLF在指导T_RM细胞发育和促进炎症方面的作用.

科学领域:

免疫学
细胞生物学
分子生物学

背景情况:

CD4+组织内存T (T_RM) 细胞对于宿主防御和慢性炎症疾病至关重要.
CD4+ T_RM细胞分化的分子驱动因素在很大程度上是未知的.

研究的目的:

确定调节CD4+T_RM细胞分化和功能的关键分子.
阐明肝白血病因子 (HLF) 在CD4+ T_RM细胞生物学中的作用.

主要方法:

研究了肝白血病因子 (HLF) 在CD4+ T_RM细胞分化中的作用.
在体内利用HLF的遗传删除来评估其对T_RM细胞生成和炎症的影响.
分析了与HLF活动相关的染色体可访问性和基因表达变化.
来自人类炎症呼吸道组织的HLF+ CD4+ T_RM细胞.

主要成果:

发现HLF可以指导CD4+T_RM细胞的组织存活程序和功能.
HLF上调的组织保留受体,下调的组织退出受体,并诱导Bhlhe40,促进促炎性CD4+T_RM细胞.
对HLF的遗传删除抑制了CD4+ T_RM细胞的产生,并减少了呼吸道炎症.
人类呼吸道组织中的HLF+ CD4+ T_RM细胞表现出存在的特征和表达的炎症性细胞因子.

结论:

作为促炎性CD4+T_RM细胞发育和功能的中心调节者.
针对HLF可能为CD4+T_RM细胞驱动的炎症疾病提供治疗策略.

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