Palomo Jennifer, Dietrich Damien, Martin Praxedis, Palmer Gaby, Gabay Cem (2015), The interleukin (IL)-1 cytokine family – Balance between agonists and antagonists in inflammatory diseases, in Cytokine
, 76(1), 25-37.
Martin Praxedis, Palmer Gaby, Rodriguez Emiliana, Woldt Estelle, Mean Isabelle, James Richard W., Smith Dirk E., Kwak Brenda R., Gabay Cem (2015), Atherosclerosis severity is not affected by a deficiency in IL-33/ST2 signalingDeficiency in IL-33 signaling does not affect atherosclerosis severity, in Immunity, Inflammation and Disease
, 3(3), 239-246.
Talabot-Ayer Dominique, Martin Praxedis, Seemayer Christian Alexander, Vigne Solenne, Lamacchia Céline, Finckh Axel, Saiji Essia, Gabay Cem, Palmer Gaby (2014), Immune-mediated experimental arthritis in IL-33 deficient mice., in Cytokine
, 69(1), 68-74.
Talabot-Ayer Dominique, Martin Praxedis G., Vesin Christian, Seemayer Christian Alexander, Vigne Solenne, Gabay Cem E M, Palmer Gaby William (2014), Severe neutrophil-dominated inflammation and enhanced myelopoiesis in IL-33-overexpressing CMV/IL33 mice, in Journal of Immunology
, 194(2), 750-760.
Martin Praxedis, Talabot-Ayer Dominique, Seemayer Christian Alexander, Vigne Solenne, Lamacchia Céline, Rodriguez Emiliana, Finckh Axel, Smith Dirk E, Gabay Cem, Palmer Gaby (2013), Disease severity in K/BxN serum transfer-induced arthritis is not affected by IL-33 deficiency., in Arthritis research & therapy
, 15(1), 13-13.
Talabot-Ayer Dominique, Gabay Cem, Palmer Gaby (2013), Reply to Xie et al. about the article "Distinct serum and synovial fluid interleukin (IL)-33 levels in rheumatoid arthritis, psoriatic arthritis and osteoarthritis"., in Joint, bone, spine : revue du rhumatisme
, 80(1), 117-8.
Talabot-Ayer Dominique, Calo Nicolas, Vigne Solenne, Lamacchia Céline, Gabay Cem, Palmer Gaby (2011), The mouse interleukin (Il)33 gene is expressed in a cell type- and stimulus-dependent manner from two alternative promoters., in Journal of leukocyte biology
, 91(1), 119-125.
Background: Interleukin (IL)-33 (or IL-1F11) is the most recently discovered member of the IL-1 cytokine family, which was identified as a ligand for the T1/ST2 receptor. IL-33 is constitutively expressed in the nucleus of endothelial and epithelial cells. In addition, IL-33 expression is induced in both resident and infiltrated cells in inflamed tissues. Consistent with expression of the T1/ST2 receptor on many cells involved in Th2 type immunity, IL-33 injection induces or amplifies Th2 type responses in various mouse models. However, IL-33 also displays pro-inflammatory effects in models which are independent of Th2 type immunity, including experimental models of arthritis. Over the last year, it has become clear that IL-33 is not, as initially thought, a caspase-1 dependent cytokine, but this interesting molecule rather emerged as a dual function protein, similar to IL-1a, displaying both nuclear and extracellular effects. However, while the extracellular, T1/ST2 dependent effects of IL-33 are being widely explored, only scarce information is available about its nuclear, T1/ST2 independent functions.Working hypothesis: Our working hypothesis is that the new IL-1 family cytokine IL-33 is involved in the inflammatory process in arthritis. In this context, we are particularly interested in defining both extracellular, T1/ST2 dependent, as well as potential nuclear functions of IL-33. Specific aims and experimental design: The purpose of our studies is to explore the respective roles of IL-33 and T1/ST2 in mouse models of arthritis in vivo. In addition, we plan to investigate nuclear effects of IL-33 in vitro in cultured myeloid cells and to analyze the regulation of IL-33 transcription. Accordingly, this proposal includes the following 3 specific aims:1. To examine the effect of IL-33 deficiency, as compared to that of T1/ST2deficiency, in three complementary models of arthritis in mice2. To investigate the nuclear functions, protein-protein and protein-DNA interactions of IL-333. To study the regulation of IL-33 mRNA expression Expected value of the proposed project: Our understanding of the role of cytokines, such as TNF-a or IL-6, in the pathogenesis of rheumatoid arthritis, has led to the development of efficacious treatments. However, a proportion of patients does not respond to treatments based on blockade of these molecules, indicating that additional mediators are involved in the pathophysiology of this disease. Recently, IL-33 emerged as an interesting dual function cytokine with both extracellular and nuclear effects. The results of the experiments described in this proposal will provide important information concerning T1/ST2 receptor dependent and independent functions of IL-33 in modulating immune responses and inflammation in vivo, as well as on the therapeutic potential of this new target in the treatment of inflammatory arthritis. Focusing on receptor-independent effects of IL-33, we will complete this work by in vitro analysis of the nuclear functions of IL-33 in activated innate immune cells. Finally, we will study the regulation of IL-33 mRNA expression.