title: Fas-associated death domain protein and adenosine partnership: fad in RA.
abstract: Inflammation is the principal hallmark of RA. Different pathways are implicated in the production of pro-inflammatory cytokines, the bona fide mediators of this inflammation. Among them are the TNF pathway and the IL-1 receptor/Toll-like receptor (IL-1R/TLR4) pathway. One of the potential negative regulators of IL-1R/TLR4 signalling is the Fas-associated death domain protein (FADD), which is the pivotal adaptor of the apoptotic signal mediated by death receptors of the TNF family. FADD can sequester myeloid differentiation primary response gene 88 (MyD88), the common adaptor of most TLRs, and hence hinder the activation of nuclear factor κB (NF-κB), the downstream transcription factor. We recently described a new regulatory mechanism of FADD expression, via the shedding of microvesicles, mediated by adenosine receptors. Interestingly, adenosine is found in high concentrations in the joints of RA patients and has been largely reported as a regulator of inflammation. This review discusses the possible link that could exist between the adenosine-dependent regulation of FADD in the inflammatory context of RA and the potential role of FADD as a therapeutic target in the treatment of RA. We will see that the modulation of FADD expression may be a double-edged sword by increasing apoptosis and at the same time limiting NF-κB activation.
authors.affiliation: Département d’Immunologie-Hématologie, Institut Cochin, Inserm U1016, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Vilmont
authors.forename: Léa
authors.initials: L
authors.lastname: Tourneur
authors.forename: Gilles
authors.initials: G
authors.lastname: Chiocchia
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism*; D053200:Fas-Associated Death Domain Protein / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction / Q000276:immunology*
chemical_list: C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D000241:Adenosine