Joslin Diabetes Center, Harvard Medical School, Boston, MA, United States.
Section on Hematopoiesis and Lymphocyte Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.
Front Immunol. 2022 Jun 2;13:906499. doi: 10.3389/fimmu.2022.906499. eCollection 2022.
CD5 is constitutively expressed on all T cells and is a negative regulator of lymphocyte function. However, the full extent of CD5 function in immunity remains unclear. CD5 deficiency impacts thymic selection and extra-thymic regulatory T cell generation, yet CD5 knockout was reported to cause no immune pathology. Here we show that CD5 is a key modulator of gut immunity. We generated mice with inducible CD5 knockdown (KD) in the autoimmune-prone nonobese diabetic (NOD) background. CD5 deficiency caused T cell-dependent wasting disease driven by chronic gut immune dysregulation. CD5 inhibition also exacerbated acute experimental colitis. Mechanistically, loss of CD5 increased phospho-Stat3 levels, leading to elevated IL-17A secretion. Our data reveal a new facet of CD5 function in shaping the T cell cytokine profile.
CD5 持续表达于所有 T 细胞上，是淋巴细胞功能的负调控因子。然而，CD5 在免疫中的功能仍不清楚。CD5 缺乏会影响胸腺选择和胸腺外调节性 T 细胞的产生，但据报道 CD5 敲除不会引起免疫病理学。在这里，我们发现 CD5 是肠道免疫的关键调节剂。我们在易发生自身免疫的非肥胖型糖尿病（NOD）背景下生成了可诱导 CD5 敲低（KD）的小鼠。CD5 缺乏导致慢性肠道免疫失调驱动的 T 细胞依赖性消耗性疾病。CD5 抑制也加重了急性实验性结肠炎。从机制上讲，CD5 的缺失增加了磷酸化 Stat3 的水平，导致 IL-17A 的分泌增加。我们的数据揭示了 CD5 功能在塑造 T 细胞细胞因子谱方面的一个新方面。
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