AITRL/TNFSF18 Protein, Mouse (HEK293, Fc)

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, Mouse (HEK293, Fc) is a recombinant mouse AITRL (T47-S173) with N-terminal hFc tag, which is expressed in HEK293.

GITRL (AITRL), a type II transmembrane protein, is a ligand for glucocorticoid-induced TNFR-related protein (GITR). GITR, a member of the TNFR superfamily, is expressed in T cells, natural killer cells and some myeloid cells^[1]. And murine GITRL has been detected on dendritic cells (DCs), monocytes, macrophages, B cells, endothelial cells, osteoclasts, and microglia cells^[4].
When GITRL binds to GITR, GITR can produce costimulatory signals that regulate T-cell proliferation and effector functions. The interaction stimulates proliferation and cytokine production of both CD4⁺ Teff and Treg cells, and drives antitumor activity of CD8⁺ T cells^[3]. Besides, GITRL plays a role in EC-activation and promotes adhesion in both mice and humans, which increases STAT-1 phosphorylation and the augmented expression of adhesion molecules such as VCAM-1 and ICAM-1^[2]. Mouse GITRL can activate signal transduction, including inducing a tolerogenic effect in DCs and pro-inflammatory stimuli in macrophages^[7].
Mouse GITRL shares < 55% common aa identity with human. Murine GITRL exists as a dimer^[4] GITR/GITRL interaction plays a role in the pathogenesis of tumor, inflammation, as well as autoimmune diseases^[1]

AITRL (mouse, 5 μg/mL, 48 h) promotes the maturation of myeloid-derived suppressor cells (MDSCs) isolated from ESS mice^[5].
AITRL (mouse, 2 μg/mL, 72 h) provides moderate costimulation to Treg cell proliferation^[6].

AITRL (mouse, 2 mg/kg, i.v.) attenuates the suppressive effect of MDSCs in ESS mice^[5].

Mouse

HEK293

N-hFc

Q7TS55 (T47-S173)

240873  [NCBI]

50-60 kDa

Greater than 95% as determined by Tris-Bis PAGE.

Lyophilized powder

Lyophilized from 0.22 μm filtered solution in PBS (pH 7.4). Normally 8% trehalose is added as protectant before lyophilization.

<1 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O.

Stored at -20°C for 2 years. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer (with carrier protein). It is recommended to freeze aliquots at -20°C or -80°C for extended storage.

Room temperature in continental US; may vary elsewhere.

• [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]

  [6]. Chen M, et al. IFN-β induces the proliferation of CD4+CD25+Foxp3+ regulatory T cells through upregulation of GITRL on dendritic cells in the treatment of multiple sclerosis. J Neuroimmunol. 2012 Jan 18;242(1-2):39-46.  [Content Brief]

  [7]. Nocentini G, et al. Pharmacological modulation of GITRL/GITR system: therapeutic perspectives. Br J Pharmacol. 2012 Apr;165(7):2089-99.  [Content Brief]