Immune privilege or inflammation? The paradoxical effects of Fas ligand

Abstract

Fas ligand (FasL) induces apoptosis of cells, including activated lymphocytes, expressing its cognate receptor, Fas (CD95/APO-1). FasL precludes inflammatory reactions from immune privileged sites by triggering Fas-mediated apoptosis of infiltrating proinflammatory cells. Aberrant expression of FasL by cancers inhibits antitumor immune responses. The ability of FasL to impair immune responses may hold therapeutic promise as a means of protecting tissue transplants from immunological rejection. Paradoxically, FasL exhibits proinflammatory activity independent of its ability to mediate immune privilege. FasL has been shown to recruit and activate neutrophils, although the factors that determine whether FasL is pro- or anti-inflammatory are only beginning to emerge. FasL appears to contribute to cell death in Fas-sensitive endorgan cells during inflammation. Blocking of Fas-mediated endorgan apoptosis or enhancing Fas-mediated apoptosis of inflammatory cells represent potential targets for future antiinflammatory therapies.