Selected Publications
- Claudia Loetsch, Joanna Warren, Christoph Jandl, Adrienne Laskowski, David Thorburn, David Ryugo, Jonathan Sprent, Marcel Batten and Cecile King (2017). Cytosolic recognition of RNA drives the immune response to heterologous erythrocytes. Cell Reports Nov 7;21(6):1624-1638. doi: 10.1016/ j.celrep.2017.10.044.
- Christoph Jandl, Sue M. Liu, Pablo F. Cañete, Joanna Warren, William E. Hughes, Alexis Vogelzang, Kylie Webster, Maria E. Craig, Gulbu Uzel, Alexander Dent, Polina Stepensky, Bärbel Keller, Klaus Warnatz, Jonathan Sprent and Cecile King (2017). IL-21 restricts regulatory T cells through Bcl-6 mediated inhibition of responsiveness to IL-2. Nature Communications Mar 17;8:14647. doi: 10.1038/ncomms14647.
- Helen McGuire, Alexis Vogelzang, Cindy S Ma, William E. Hughes, Pablo Silveira, Stuart G Tangye, David Fulcher, Daniel Christ, Marika Falcone and Cecile King (2011). A Subset of Interleukin-21(+) Chemokine Receptor CCR9(+) T Helper Cells Target Accessory Organs of the Digestive System in Autoimmunity. Immunity, 2011 Apr 22;34(4):602-15.
- Alexis Vogelzang, Helen M. McGuire, Jon Sprent Charles R. Mackay and Cecile King (2008). A fundamental role for IL-21 in T helper cell differentiation. Immunity, Jul;29(1):127-37.
FRIAS Project
Interleukin-21 induced formation of STAT1 and STAT3 dimers.
Our bodies rely on the production of antibodies to fight infection. In simple terms, our immune system contains B cells, which make antibodies, T cells, which help them and chemical messengers known as ‘cytokines’ that modulate this process. The cytokine IL-21 is produced by specialised cells known as T follicular helper cells, which help select B cells that produce the most potent antibodies. When IL-21 binds to its receptor (IL-21R) on the surface of a cell, it activates signals inside the cell to influence its behaviour, namely the Jak/STAT signalling pathway- through the phosphorylation of the proteins STAT1 and STAT3. We have generated a novel mouse that contains a single mutation in the IL-21R (Il21rEINS) that diminishes STAT1 activation, with no effect on STAT3. This minor genetic lesion had the fascinating outcome of dampening down the immune response. HYPOTHESES: IL-21 induces the activation of STAT1 and STAT3 proteins that form hetero- and homodimers that impart their functions on cell fate by binding to DNA and influencing gene transcription. We hypothesise that the formation of STAT dimers is influenced by the relative abundance of different forms of activated STAT proteins. RESEARCH PLAN: We will take advantage of Signalling and Immunological expertise at Freiburg University to analyse the formation of STAT dimers in the context of IL-21:IL-21 signalling in human cells with mutations in STAT signalling.