AITRL/TNFSF18 蛋白, Human (sf9, His)

AITRL, a type II transmembrane protein, is a ligand for glucocorticoid-induced TNFR-related protein (GITR). When AITRL binds to GITR, GITR can produce costimulatory signals that regulate T-cell proliferation and effector functions. GITR/AITRL interaction plays a role in the pathogenesis of tumor, inflammation, as well as autoimmune diseases^[1]. Besides, AITRL plays a role in endothelial cells (EC)-activation and increases STAT-1 phosphorylation and the expression of adhesion molecules (VCAM-1, ICAM-1)^[2]. AITRL/TNFSF18 Protein, Human (sf9, His) is a recombinant human AITRL (E52-S177) with N-terminal His tag, which is expressed in Sf9 insect cells.

GITRL (AITRL) 是一种 II 型跨膜蛋白，是糖皮质激素诱导的 TNFR 相关蛋白 (GITR) 的配体。GITR 是 TNFR 超家族的成员，在 T 细胞、自然杀伤细胞和一些骨髓细胞中表达。而GITRL主要表达于抗原呈递细胞（B细胞、树突状细胞）、巨噬细胞和内皮细胞（EC）^[1]。
当GITRL与GITR结合时，GITR可产生共刺激信号调节 T 细胞增殖和效应功能。这种相互作用刺激 CD4⁺ Teff 和 Treg 细胞的增殖和细胞因子产生，并驱动 CD8⁺ T 细胞^[3]的抗肿瘤活性。此外，GITRL 在 EC 激活中发挥作用，并促进小鼠和人类的粘附，从而增加 STAT-1 磷酸化并增强 VCAM-1 和 ICAM-1 等粘附分子的表达^[2]。
人类 GITRL 与小鼠的共同氨基酸一致性< 55%。人 GITRL 由胞质结构域 (M1-W27)、螺旋结构域 (L28-F48) 和胞外结构域 (L49-S177) 组成。人GITRL是一个三聚体，但也可以是单体或组装成其他多聚体结构^[4]。
GITR/GITRL相互作用在肿瘤、炎症等的发病机制中发挥着重要作用作为自身免疫性疾病^[1]。

AITRL (human, 48 h) reduces the suppressive capacity of MDSCs on CD4⁺ T cells (MDSCs induced from healthy donors)^[5].

Human

Sf9 insect cells

N-His

Q9UNG2/AAD22634 (E52-S177)

8995  [NCBI]

Approximately 15.6 kDa

Greater than 95% as determined by reducing SDS-PAGE.

<1 EU/μg, determined by LAL method.

• [1]. Tian J, et al. The Role of GITR/GITRL Interaction in Autoimmune Diseases. Front Immunol. 2020 Oct 9;11:588682.  [Content Brief]

  [2]. Lacal PM, et al. Glucocorticoid-induced tumor necrosis factor receptor family-related ligand triggering upregulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 and promotes leukocyte adhesion. J Pharmacol Exp Ther. 2013 Oct;347(1):164-72.  [Content Brief]

  [3]. Wang F, et al. Structures of mouse and human GITR-GITRL complexes reveal unique TNF superfamily interactions. Nat Commun. 2021 Mar 2;12(1):1378.  [Content Brief]

  [4]. Placke T, et al. Glucocorticoid-induced TNFR-related (GITR) protein and its ligand in antitumor immunity: functional role and therapeutic modulation. Clin Dev Immunol. 2010;2010:239083.  [Content Brief]

  [5]. Tian J, et al. Increased GITRL Impairs the Function of Myeloid-Derived Suppressor Cells and Exacerbates Primary Sjögren Syndrome. J Immunol. 2019 Mar 15;202(6):1693-1703.  [Content Brief]