The interleukin 12 (IL-12) family of cytokines regulates T cell functions and is key for the orchestration of immune responses. Each heterodimeric IL-12 family member is a glycoprotein. However, the impact of glycosylation on biogenesis and function of the different family members has remained incompletely defined.

Here, we identify glycosylation sites within human IL-12 family subunits that become modified upon secretion. Building on these insights, we show that glycosylation is dispensable for secretion of human IL-12 family cytokines except for IL-35. Furthermore, our data show that glycosylation differentially influences IL-12 family cytokine functionality, with IL-27 being most strongly affected.

Taken together, our study provides a comprehensive analysis of how glycosylation affects biogenesis and function of a key human cytokine family and provides the basis for selectively modulating their secretion via targeting glycosylation.

白细胞介素12（IL-12）细胞因子家族调节T细胞功能，是协调免疫反应的关键。每个异二聚体IL-12家族成员都是糖蛋白。但是，糖基化对不同家族成员的生物发生和功能的影响尚未完全确定。

在这里，我们确定了人类IL-12家族亚基中的糖基化位点，这些位点在分泌后会被修饰。基于这些见解，我们显示糖基化对于除IL-35以外的人IL-12家族细胞因子的分泌都是不可或缺的。此外，我们的数据显示糖基化差异影响IL-12家族细胞因子的功能，其中IL-27受的影响最大。

综上所述，我们的研究提供了糖基化如何影响关键人类细胞因子家族的生物发生和功能的全面分析，并为通过靶向糖基化选择性调节其分泌提供了基础。