Mapping the Interleukin-27 signalosome – from cell surface receptors to T-cell differentiation

Cytokines are key regulators of innate and adaptive immunity as well as haematopoiesis. Binding of these soluble messenger proteins to tissue-specific cell surface receptors activates signalling cascades which lead to regulation of target gene expression patterns.

Interleukin 27 (IL-27) and Interleukin-6 belong to the IL-6/IL-12 superfamily. Although many members of this family share the same set of receptors and JAK/STAT effectors, their downstream effects can even be opposing: IL-27 is considered be a key regulator for anti-inflammatory effects, IL-6 is a paradigm cytokine for pro-inflammatory responses. So, the differential outcome of these responses must be encoded in the early events of signal activation. Using different approaches (single molecule TIRF imaging, high throughput phospho-flow cytometry and mass spectrometry-based proteomics), we specifically aim to identify the molecular determinants underlying functional selectivity of IL-27 signalling on T cells.