TP4: Modulation of experimental autoimmune encephalitis by the regulatory T cell-derived cytokine interleukin-35

Fine-tuning of cell-mediated inflammatory immune response is primarily mediated by interleukin (IL)-12-related cytokines. Members of this cytokine family have a unique dimeric structure and so far primarily activated macrophages and dendritic cells have been described to produce IL-12 family dimers. Whereas the recently described IL-27 consists of the

IL-27p28 and the Epstein-Barr virus-induced gene 3 (EBI3) subunit, the IL-12p40-related cytokines, IL-12 and IL-23 share the IL-12p40 subunit. In contrast to IL-12 and IL-23, which are required for the development of CD4+ T helper (TH) 1 and TH17 immune responses, respectively, IL-27 has been shown to suppress cell-mediated inflammation. In contrast to TH1 and TH17 cells, regulatory T (Treg) cells are a critical sub-population of CD4+ T cells that are important to prevent autoimmunity and to limit chronic inflammatory diseases but they also suppress protective immune responses to pathogens as well as anti-tumour immunity. However, molecules that mediate their suppressive activity remain largely unknown. Very recently, a new member of the IL-12 cytokine family, IL-35, was discovered. This cytokine consists of the EBI3 and the IL-12p35 subunit and in contrast to all other IL-12 family dimers, IL-35 is exclusively produced by Treg cells. On a functional level, Treg-derived IL-35 has been described to suppress cell-mediated inflammatory immune responses. Because Treg cells modulate TH1 and TH17 inflammatory immune responses that are involved in the regulation of the immunopathology in experimental autoimmune encephalitis (EAE), the experimental model for human multiple sclerosis, we therefore are interested to analyse the function of these IL-35-mediated regulatory mechanisms exerted by Treg cells in vivo. 

Due to a publication on the same topic, this project was re-focused. Now we are investigating similar mechanisms in EBA. This project will be continued in TP A3, where we will investigate the role of IL-17 in the loss of tolerance in EBA. 

Melanie graduated in January 2017. Congratulations!