Hagenstein Julia, Burkhardt Simon, Sprezyna Paulina, Tasika Elena, Tiegs Gisa, Diehl Linda
Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
Hamburg Center of Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
J Leukoc Biol. 2024 Jun 28;116(1):177-185. doi: 10.1093/jleuko/qiae053.
In chronic inflammation, regulatory immune cells, such as regulatory T cells and myeloid-derived suppressor cells, can develop. Local signals in the inflamed tissue, such as cytokines and eicosanoids, but also contact-dependent signals, can promote myeloid-derived suppressor cell development. In the liver, hepatic stellate cells may provide such signals via the expression of CD44. Myeloid-derived suppressor cells generated in the presence of hepatic stellate cells and anti-CD44 antibodies were functionally and phenotypically analyzed. We found that both monocytic and polymorphonuclear myeloid-derived suppressor cells generated in the presence of αCD44 antibodies were less suppressive toward T cells as measured by T-cell proliferation and cytokine production. Moreover, both monocytic and polymorphonuclear myeloid-derived suppressor cells were phenotypically altered. Monocytic myeloid-derived suppressor cells mainly changed their expression of CD80 and CD39, and polymorphonuclear myeloid-derived suppressor cells showed altered expression of CD80/86, PD-L1, and CCR2. Moreover, both polymorphonuclear and monocytic myeloid-derived suppressor cells lost expression of Nos2 messenger RNA, whereas monocytic myeloid-derived suppressor cells showed reduced expression of TGFb messenger RNA and polymorphonuclear myeloid-derived suppressor cells reduced expression of Il10 messenger RNA. In summary, the presence of CD44 in hepatic stellate cells promotes the induction of both monocytic and polymorphonuclear myeloid-derived suppressor cells, although the mechanisms by which these myeloid-derived suppressor cells may increase suppressive function due to interaction with CD44 are only partially overlapping.
在慢性炎症中，可产生调节性免疫细胞，如调节性T细胞和髓系来源的抑制性细胞。炎症组织中的局部信号，如细胞因子和类花生酸，以及接触依赖性信号，均可促进髓系来源的抑制性细胞的产生。在肝脏中，肝星状细胞可能通过CD44的表达提供此类信号。对在肝星状细胞和抗CD44抗体存在下产生的髓系来源的抑制性细胞进行了功能和表型分析。我们发现，通过T细胞增殖和细胞因子产生测定，在αCD44抗体存在下产生的单核细胞和多形核髓系来源的抑制性细胞对T细胞的抑制作用均较弱。此外，单核细胞和多形核髓系来源的抑制性细胞在表型上均发生了改变。单核细胞髓系来源的抑制性细胞主要改变了其CD80和CD39的表达，多形核髓系来源的抑制性细胞则显示出CD80/86、PD-L1和CCR2表达的改变。此外，多形核和单核细胞髓系来源的抑制性细胞均失去了Nos2信使核糖核酸的表达，而单核细胞髓系来源的抑制性细胞显示出TGFb信使核糖核酸表达降低，多形核髓系来源的抑制性细胞Il10信使核糖核酸表达降低。总之，肝星状细胞中CD44的存在促进了单核细胞和多形核髓系来源的抑制性细胞的诱导，尽管这些髓系来源的抑制性细胞由于与CD44相互作用而可能增强抑制功能的机制仅部分重叠。
