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TRAIL and FasL Functions in Cancer and Autoimmune Diseases: Towards an Increasing Complexity

Université Côte d’Azur, CNRS, Inserm, iBV, 06108 Nice, France
Authors to whom correspondence should be addressed.
Cancers 2019, 11(5), 639;
Received: 4 April 2019 / Revised: 26 April 2019 / Accepted: 28 April 2019 / Published: 8 May 2019
(This article belongs to the Special Issue TRAIL Signaling in Cancer Cells)
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Tumor Necrosis Factor-Related Apoptosis Inducing Ligand (TRAIL/TNFSF10) and Fas Ligand (FasL/TNFSF6), two major cytokines of the TNF (Tumor Necrosis Factor) superfamily, exert their main functions from the immune system compartment. Mice model studies revealed that TRAIL and FasL-mediated signalling both control the homeostasis of the immune cells, mainly from the lymphoid lineage, and function on cytotoxic cells as effector proteins to eliminate the compromised cells. The first clues in the physiological functions of TRAIL arose from the analysis of TRAIL deficient mice, which, even though they are viable and fertile, are prone to cancer and autoimmune diseases development, revealing TRAIL as an important safeguard against autoimmunity and cancer. The naturally occurring gld (generalized lymphoproliferative disease) and lpr (lymphoproliferation) mutant mice develop lymphadenopathy and lupus-like autoimmune disease. The discovery that they are mutated in the fasl and the fas receptor gene, respectively, demonstrates the critical role of the FasL/Fas system in lymphocyte homeostasis and autoimmunity. This review summarizes the state of current knowledge regarding the key death and non-death immune functions that TRAIL and FasL play in the initiation and progression of cancer and autoimmune diseases.
Keywords: death receptors; autoimmunity; cancer; immune system; cell death death receptors; autoimmunity; cancer; immune system; cell death
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Rossin, A.; Miloro, G.; Hueber, A.-O. TRAIL and FasL Functions in Cancer and Autoimmune Diseases: Towards an Increasing Complexity. Cancers 2019, 11, 639.

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