The State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China.
Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Commun Biol. 2021 Mar 16;4(1):344. doi: 10.1038/s42003-021-01877-w.
Adiponectin is a well-known insulin sensitizer and anti-inflammatory molecule, possessing therapeutic potentials in cardiovascular, metabolic and cancer diseases. Results of the present study demonstrate that adiponectin is expressed in a population of regulatory T-cells (Treg) resided within the thymic nurse cell (TNC) complexes. Adoptive transfer of adiponectin-expressing Treg precursors effectively attenuated obesity, improved glucose and insulin tolerance, prevented fatty liver injuries in wild-type mice fed a high-fat diet, and significantly inhibited breast cancer development in MMTV-PyVT transgenic mice. Within the TNC complexes, locally produced adiponectin bound to and regulated the expression as well as the distribution of CD100, a transmembrane lymphocyte semaphorin, in turn modulating the lymphoepithelial interactions to facilitate T-cell development and maturation. In summary, adiponectin plays an important role in the selection and development of T lymphocytes within the TNC complexes. Adiponectin-expressing Treg represent a promising candidate for adoptive cell immunotherapy against obesity-related metabolic and cancer diseases.
脂联素是一种众所周知的胰岛素增敏因子和抗炎分子，在心血管、代谢和癌症疾病中具有治疗潜力。本研究结果表明，脂联素在胸腺滋养细胞（TNC）复合体中存在于一群调节性 T 细胞（Treg）中表达。过继转移表达脂联素的 Treg 前体可有效减轻肥胖、改善葡萄糖和胰岛素耐量、预防高脂肪饮食喂养的野生型小鼠的脂肪肝损伤，并显著抑制 MMTV-PyVT 转基因小鼠的乳腺癌发生。在 TNC 复合体中，局部产生的脂联素与跨膜淋巴细胞信号素 CD100 结合并调节其表达和分布，从而调节淋巴上皮相互作用，促进 T 细胞的发育和成熟。总之，脂联素在 TNC 复合体中 T 淋巴细胞的选择和发育中发挥重要作用。表达脂联素的 Treg 代表了针对肥胖相关代谢和癌症疾病的过继细胞免疫治疗的有希望的候选者。
