Induction of tolerance using Fas ligand: A double-edged immunomodulator

Nadir Askenasy*, Esma S. Yolcu, Isaac Yaniv, Haval Shirwan

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


Apoptosis mediated by Fas ligand (FasL) interaction with Fas receptor plays a pivotal regulatory role in immune homeostasis, immune privilege, and self-tolerance. FasL, therefore, has been extensively exploited as an immunomodulatory agent to induce tolerance to both autoimmune and foreign antigens with conflicting results. Difficulties associated with the use of FasL as a tolerogenic factor may arise from (1) its complex posttranslational regulation, (2) the opposing functions of different forms of FasL, (3) different modes of expression, systemic versus localized and transient versus continuous, (4) the level and duration of expression, (5) the sensitivity of target tissues to Fas/FasL-mediated apoptosis and the efficiency of antigen presentation in these tissues, and (6) the types and levels of cytokines, chemokines, and metalloproteinases in the extracellular milieu of the target tissues. Thus, the effective use of FasL as an immunomodulator to achieve durable antigen-specific immune tolerance requires careful consideration of all of these parameters and the design of treatment regimens that maximize tolerogenic efficacy, while minimising the non-tolerogenic and toxic functions of this molecule. This review summarizes the current status of FasL as a tolerogenic agent, problems associated with its use as an immunomodulator, and new strategies to improve its therapeutic potential.

Original languageEnglish
Pages (from-to)1396-1404
Number of pages9
Issue number4
StatePublished - 15 Feb 2005


FundersFunder number
National Institute of Allergy and Infectious DiseasesR21AI057903, R01AI047864
National Institute of Diabetes and Digestive and Kidney DiseasesR21DK061333


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