IMI - Institute for Medical Immunology

Regulation of interleukin-12 family members synthesis downstream of pattern recognition receptors

Summary

Interleukin (IL)-12 and the related heterodimeric cytokines IL-23 and IL-27 are mainly produced by dendritic cells upon stimulation of Pattern Recognition Receptors (PRR). These three cytokines play critical and distinct roles in shaping the innate and adaptive immune responses in the course of infection, cancer or auto-immune disorder. The aim of this project is to identify vaccination strategies that can influence the IL-12/IL-23/IL- 27 balance in order to improve immune responses while limiting the risk of associated auto-immune disorders. We previously showed that the transcription factor IRF-3 is involved in TLR4-mediated IL-12 and IL-27 production. This research project further explores the molecular mechanisms involved in the differential regulation of these cytokines and analyses the implication of signaling pathways in the control of inflammation.

Research team

Principal investigator: Stanislas GORIELY (MD-PhD)
Post-doctoral fellow: Tong ZHANG-RONSE
PhD student: Céline MOLLE
MD-PhD students: Laure YSEBRANT, Nathalie COMPTE, Rani CAVOY
Technical assistant: Muriel NGUYEN

External collaborators

M. MOSER, IBMM, ULB
V. KRUYS, IBMM, ULB
B. MALISSEN, CIML, Marseille, France

Key references

Goriely S, Cavoy R, Goldman M. Interleukin-12 family members and type I interferons in Th17-mediated inflammatory disorders. Allergy 2009; 64:702-709

Goriely S, Neurath M, Goldman M. How microorganisms tip the balance between interleukin-12 family members. Nature Rev Immunol 2008; 8: 82-86

Goriely S, Goldman M. From tolerance to autoimmunity: is there a risk in early life vaccination? J Comp Pathol 2007; 137: S57-61

Molle C, Nguyen M, Flamand V, Renneson J, Trottein F, De Wit D, Willems F, Goldman M, Goriely S. IL-27 synthesis induced by TLR ligation critically depends on IFN regulatory factor 3. J Immunol 2007; 178: 7607-7615

Goriely S, Molle C, Nguyen M, Albarani V, Ouled Haddou N, Lin R, De Wit D, Flamand V, Willems F, Goldman M. Interferon regulatory factor 3 is involved in Toll like receptor (TLR)4- and TLR3-induced IL-12p35 gene activation. Blood 2006; 107: 1078-1084