Department of Microbiology and Immunology, Loyola University, Chicago, Illinois, USA.
Department of Biology, Faculty of Science, Shizuoka University, Shizuoka, Japan.
Eur J Immunol. 2022 Jul;52(7):1077-1094. doi: 10.1002/eji.202149633. Epub 2022 May 11.
Th1 and Th2 polarization is determined by the coordination of numerous factors including the affinity and strength of the antigen-receptor interaction, predominant cytokine environment, and costimulatory molecules present. Here, we show that Schnurri (SHN) proteins have distinct roles in Th1 and Th2 polarization. SHN2 was previously found to block the induction of GATA3 and Th2 differentiation. We found that, in contrast to SHN2, SHN3 is critical for IL-4 production and Th2 polarization. Strength of stimulation controls SHN2 and SHN3 expression patterns, where higher doses of antigen receptor stimulation promoted SHN3 expression and IL-4 production, along with repression of SHN2 expression. SHN3-deficient T cells showed a substantial defect in IL-4 production and expression of AP-1 components, particularly c-Jun and Jun B. This loss of early IL-4 production led to reduced GATA3 expression and impaired Th2 differentiation. Together, these findings uncover SHN3 as a novel, critical regulator of Th2 development.
Th1 和 Th2 极化是由许多因素协调决定的，包括抗原受体相互作用的亲和力和强度、主要细胞因子环境和共刺激分子的存在。在这里，我们表明 Schnurri（SHN）蛋白在 Th1 和 Th2 极化中具有不同的作用。SHN2 先前被发现可阻断 GATA3 的诱导和 Th2 分化。我们发现，与 SHN2 相反，SHN3 对 IL-4 的产生和 Th2 极化至关重要。刺激的强度控制 SHN2 和 SHN3 的表达模式，其中较高剂量的抗原受体刺激促进了 SHN3 的表达和 IL-4 的产生，同时抑制了 SHN2 的表达。SHN3 缺陷型 T 细胞在 IL-4 的产生和 AP-1 成分的表达，特别是 c-Jun 和 Jun B 方面表现出明显缺陷。这种早期 IL-4 产生的丧失导致 GATA3 表达减少和 Th2 分化受损。总之，这些发现揭示了 SHN3 是 Th2 发育的一个新的关键调节因子。
