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World J Rheumatol. Aug 3, 2012; 2(1): 1-11
Published online Aug 3, 2012. doi: 10.5499/wjr.v2.i1.1
Role of Apo2L/TRAIL in immunity: Applications to rheumatoid arthritis
Luis Martinez-Lostao, Alberto Anel
Luis Martinez-Lostao, Alberto Anel, Department of Biochemistry, Molecular and Cell Biology, Faculty of Science, University of Zaragoza, Zaragoza 50009, Spain
Author contributions: Martinez-Lostao L and Anel A solely contributed to this paper.
Supported by the Ministerio de Ciencia e Innovación No. SAF2007-16674 and No. SAF2010-15341 to Anel A; and a Sara Borrell Postdoctoral Contract No. CD05/00082 from the Instituto de Salud Carlos III, Spain to Martinez-Lostao L
Correspondence to: Luis Martinez-Lostao, MD, PhD, Departamento de Bioquímica, Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, C/Pedro Cerbuna 12, Zaragoza 50009, Spain. lumartin@unizar.es
Telephone: +34-976-762301 Fax: +34-976-762123
Received: June 2, 2011
Revised: April 18, 2012
Accepted: July 4, 2012
Published online: August 3, 2012

Rheumatoid arthritis (RA) is the most common inflammatory disease of the musculoskeletal system primarily affecting the joints. It is characterized by massive synovial hyperplasia and subsequent destruction of articular cartilage and bone. Although various aspects in the pathogenesis of RA remain unclear, genetic, environmental and of course immunological factors have been involved. Defects in apoptosis seem to play a role in both initiation and perpetuation of RA. Apo2 ligand/ tumor necrosis factor (TNF) related apoptosis-inducing ligand (Apo2L/TRAIL) is a cytokine that belongs to the TNF superfamily capable of inducing apoptosis on tumor cells through activation of the extrinsic pathway. Besides this function, like other members of the TNF superfamily, Apo2L/TRAIL has been shown to exert important functions in the regulation of the immune system. Concerning pathological conditions, the Apo2L/TRAIL signaling pathway plays an important role in the response to infections, in immune surveillance against tumors and in autoimmune diseases such as RA. Furthermore, its implication in suppression of autoimmunity suggests that Apo2L/TRAIL has potential as therapeutic agent not only in cancer but also in autoimmune diseases. In fact, Apo2L/TRAIL-based therapies have been shown effective in various animal models of RA. This review summarizes the current knowledge on the biology of Apo2L/TRAIL and its role in RA.

Keywords: Apo2 ligand, Tumor necrosis factor related apoptosis-inducing ligand, Apoptosis, Rheumatoid arthritis, Autoimmunity, Immune response