FASLG Research Reagents

FASLG Background

FASLG gene encodes FAS ligand, a homotrimeric type II transmembrane protein belonging to the tumor necrosis factor (TNF) family ^[1]. FASLG is also called FASL, CD95L, or TNFSF6 (Tumor necrosis factor ligand superfamily member 6). FASL is mainly expressed in activated T lymphocytes and Natural Killer (NK) cells ^[2][3] and also has constitutive expression in immune-privileged sites such as the eyes and testis ^[4][5]. Bossi G and Griffiths GM found that FasL is stored in specialized secretory lysosomes in T cells and NK cells after synthesis, and the delivery of FasL to the cell surface may be associated with activation of these cells ^[6]. It has been reported that the cytoplasmic tail of FasL transduces the proliferation signal in CD8-T cells ^[7] and propagates a signal to arrest the cell cycle in CD4-T cells ^[8]. In the Fas-mediated apoptotic pathway, binding of FasL drives Fas clustering and binding of Fas to FADD. FADD recruits caspase-8 and caspase-10 to form the death-inducing signaling complex (DISC), triggering the cleavage of several pro-caspases and eventually inducing apoptosis ^[9]. In addition to its role in apoptosis, FASL is involved in immune privilege ^[5] and a cytotoxic T lymphocyte (CTL)-induced tissue destruction ^[10]. Significantly increased levels of FASL is detected in numerous diseases such as hemophagocytic syndrome ^[11], Diamond-Blackfan anemia ^[11], rheumatoid arthritis ^[13], myocarditis ^[12], and acute GvHD (graft-versus-host disease) ^[14].

[1] Suda T, Takahashi T, et al. Molecular cloning and expression of the Fas ligand: a novel member of the tumor necrosis factor family [J]. Cell 1993, 75: 1169– 78.
[2] Oshimi Y, Oda S, et al. Involvement of Fas ligand- and Fas-mediated pathway in the cytotoxicity of human natural killer cells [J]. J. Immunol. 1996, 157: 2909– 15.
[3] Suda T, Okazaki T, et al. Expression of the Fas ligand in T-cell-lineage [J]. J. Immunol. 1995, 154: 3806– 1.
[4] Griffith TS, Brunner T, et al. Fas ligand-induced apoptosis as a mechanism of immune privilege [J]. Science 1995, 270: 1189– 92.
[5] Green DR, Ferguson TA. The role of Fas ligand in immune privilege [J]. Nat Rev Mol Cell Biol 2001, 2:917–24.
[6] Bossi G, Griffiths GM. Degranulation plays an essential part in regulating cell surface expression of Fas ligand in T cells and natural killer cells [J]. Nat. Med. 1999, 5: 90– 96.
[7] Suzuki I, Fink PJ. Maximal proliferation of cytotoxic T lymphocytes requires reverse signaling through Fas ligand [J]. J. Exp. Med. 1998, 187:123–28.
[8] Alnemri ES, Livingston DJ, et al. Human ICE/CED-3 protease nomenclature [J]. Cell 1996, 87:171.
[9] Nagata S. Fas ligand-induced apoptosis [J]. Annu Rev Genet 1999, 33:29–55.
[10] Nagata S, Golstein P. The Fas death factor [J]. Science 1995, 267: 1449– 56.
[11] Hasegawa D, Kojima S, et al. Elevation of the serum Fas ligand in patients with hemophagocytic syndrome and Diamond-Blackfan anemia [J]. Blood 1998, 91: 2793– 99.
[12] Toyozaki T, Hiroe M, et al. Levels of soluble Fas ligand in myocarditis [J]. Am. J. Cardiol. 1998, 82: 246– 48.
[13] Nozawa K, Kayagaki N, et al. Soluble Fas (APO-1, CD95) and soluble Fas ligand in rheumatic diseases [J]. Arthritis Rheum. 1997, 40: 1126– 29.
[14] Kanda Y, Tanaka Y, et al. Increased soluble Fas-ligand in sera of bone marrow transplant recipients with acute graft-versus-host disease [J]. Bone Marrow Transplant. 1998, 22: 751– 54.