Division of Immunity and Pathogenesis, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, 32827, USA.
NanoScience Technology Center, University of Central Florida, Orlando, USA.
Sci Rep. 2020 Jul 29;10(1):12668. doi: 10.1038/s41598-020-69632-5.
Interleukin-2 (IL-2) has both pro- and anti-inflammatory properties that have been harnessed clinically and that are used experimentally to modulate leukocyte subsets in vivo. In mice, the bioavailability and half-life of IL-2 in vivo can be increased by complexing recombinant IL-2 with different clones of anti-IL-2 monoclonal antibodies that differentially target the cytokine to cells expressing different kinds of IL-2 receptors. While the impacts of systemic IL-2: anti-IL-2 antibody complex (IL-2C) administration are well-defined in the spleen and peripheral lymph nodes, how immune cells in the gut and gut-associated lymphoid tissues respond to IL-2C is not well characterized. Here, we analyze how major leukocyte populations in these tissues respond to IL-2C. We find that IL-2C targeting cells expressing IL-2 receptor beta cause an acute decrease in cellularity of Peyer's Patches while cell numbers in the lamina propria and intraepithelial lymphocytes are unaffected. Cell contraction in Peyer's Patches is associated with the apoptosis of multiple B cell subsets. Our results are important to consider for understanding off-target impacts of IL-2C regimes in experimental models and for considering how IL-2 may contribute to the etiology or severity of gut-associated conditions such as Crohn's Disease.
白细胞介素 2（IL-2）具有促炎和抗炎特性，已在临床上得到应用，并在实验中用于调节体内白细胞亚群。在小鼠中，通过将重组 IL-2 与针对表达不同类型 IL-2 受体的细胞的不同抗 IL-2 单克隆抗体的克隆进行复合，可以增加体内 IL-2 的生物利用度和半衰期。虽然系统给予白细胞介素 2：抗白细胞介素 2 抗体复合物（IL-2C）在脾脏和外周淋巴结中的影响已得到很好的定义，但肠道和肠道相关淋巴组织中的免疫细胞如何对 IL-2C 作出反应尚不清楚。在这里，我们分析了这些组织中的主要白细胞群如何对 IL-2C 作出反应。我们发现，IL-2C 靶向表达白细胞介素 2 受体β的细胞会导致派尔集合淋巴结的细胞数量急性减少，而固有层和上皮内淋巴细胞的数量不受影响。派尔集合淋巴结中的细胞收缩与多种 B 细胞亚群的凋亡有关。我们的研究结果对于理解实验模型中 IL-2C 方案的脱靶影响以及考虑 IL-2 如何有助于肠道相关疾病（如克罗恩病）的病因或严重程度非常重要。
