IFN-gamma R2  (干扰素-γ 受体 2)

IFN-gamma R2，IFN-gamma 受体的亚基之一，是 IFN-γ 的结合受体。IFN-gamma R2 是IFN-gamma 受体的信号转导链，IFN-gamma R2 可以与 IFN-gamma R2 结合形成功能性受体。与配体 IFN-γ 结合后，IFN-gamma R2 和 IFN-gamma R1 寡聚化并发生磷酸化^[1]。然后，下游的信号分子 JAK1 和 JAK2 发生磷酸化并激活，为 STAT1 创建了一个结合位点。磷酸化的 STAT1 导致二聚化并易位至细胞核，从而调节 IFN-反应性的基因 (例如 CD54) 的表达^[2]。人 IFN-gamma R1 由细胞外结构域 (S18-Q245)、螺旋结构域 (V248-F268) 和细胞质结构域 (L269-L337) 组成。IFN-gamma R1几乎在所有细胞的表面表达^[1]。IFN-gamma R2 表达处于低水平，其表达受细胞分化或激活状态的调节。IFN-gamma R2 在骨髓细胞上高度表达，在 B 细胞上中度表达，在 T 细胞上低表达。 IFN-gamma R2 的表达水平决定 Th1-Th2 表型转换并调节随后的免疫反应^[1][2]。IFN-gamma R2 对于触发先天免疫对分枝杆菌感染的防御很重要。IFN-gamma R2 缺乏会造成孟德尔对分枝杆菌病 (MSMD) 的易感性^[2]。

IFN-gamma R2, one of the subunit of IFN-gamma receptor, is a receptor for IFN-gamma. IFN-gamma R2 is the signal-transducing chain of the IFN-gamma receptor. IFN-gamma R2 can associate with IFN-gamma R1 to form a functional receptor. Upon binding with IFN-gamma, IFNγR2 and IFNγR1 oligomerize and transphosphorylate^[1]. Then, the downstream signaling components JAK1 and JAK2 are phosphorylated and activated, thereby creating a binding site for STAT1. Phosphorylated STAT1 leads to dimerization and translocates to the nucleus, where it regulates the expression of IFN-responsive genes (e.g. CD54)^[2]. Human IFN-gamma R2 consists of extracellular domain (S28-Q247), helical domain (V248-F268), and cytoplasmic domain (L269-L337). IFN-gamma R2 is constitutively expressed at low levels, and the expression is regulated by the state of cellular differentiation or activation. IFN-gamma R2 is highly expressed on myeloid cells, moderately on B cells and low on T cells. The expression of IFN-gamma R2 can dictate the Th1–Th2 phenotype switch and modulate the subsequent immune response^[1][2]. IFN-gamma R2 is important for innating immune defense against mycobacterial infections. Defects in IFN-gamma R2 caused mendelian susceptibility to mycobacterial disease (MSMD)^[2].

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