Speaker: A/Prof Meredith O'Keeffe
NHMRC Senior Research Fellow
Department Biochemistry & Molecular Biology
The IFN-lambda (l) cytokine family is encoded by 2 genes in mouse (IFN-l2 and IFN-l3) and a total of 4 genes in humans, (l1-l4). IFN- l demonstrates potent anti-viral activity against several viruses, mediated by STAT signalling via the novel IFN- l receptor, a heterodimer of the IL-10Rb and the novel IL-28RA chain. Signalling via the IFN- l receptor leads to the expression of ISGs that resemble those induced by type I IFNs (IFN-I). However, the receptor for IFN-l exhibits highly restricted expression. It is expressed by neutrophils and it is also expressed by hepatocytes and throughout epithelial surfaces including in the intestine, kidney and skin. Moreover, the receptor is expressed by dendritic cells (DC) in the steady state and this is further upregulated during DC activation.
Plasmacytoid (p) DC produce IFN-l in response to TLR9 ligands. Mouse CD8+ and human CD141+ conventional (c) DC1 subsets share the unique ability to produce large amounts of IFN- l in response to TLR3 ligands and DNA viruses. We have investigated the role of IFN-l in DC development and function in the steady state and in settings of inflammation.
Our findings indicate that IFN-l signalling is required in DC for optimal responses to TLR ligands in vivo. IFN-lambda signalling is required for optimal antigen presentation and enhances the activation of T cells by human DC.
We have investigated the potential role of IFN-l produced by DC in autoimmune settings. Data on a cohort of SLE patients from the Monash Lupus Clinic will be presented.
Associate Professor Meredith O'Keeffe is an NHMRC Senior Research Fellow and Head of the Laboratory of Dendritic Cell Driven Immunity in Health and Disease, Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University. Meredith received her PhD from Monash University in 1998 and then spent 6 years in the laboratory of Prof Ken Shortman, WEHI where she was trained in dendritic cell biology. She then set up a dendritic cell research lab at Bavarian-Nordic GmbH, Munich, Germany and returned to Australia in 2009, setting up a lab at the Burnet Institute, Melbourne. Meredith joined the Department of Biochemistry and Molecular Biology at the end of 2015.
Meredith's current research interests include investigating the function of dendritic cells in Lupus disease and malaria infection and examining the development and function of dendritic cells in Myelodysplasia.
Dendritic cells are sentinels of the immune system that produce cytokines and interferons upon sensing danger. They are also professional antigen presenting cells, thereby connecting the innate and adaptive immune systems. Our laboratory investigates how pathogens and their products and/or or self-nucleic acids activate dendritic cells. We aim to decipher how this activation influences the function of dendritic cells. We investigate how this process may differ in different body locations, at different ages and in different disease settings. Major aims are to understand the role of dendritic cells in bone marrow malignancies and in autoimmune diseases such as Lupus.
Please contact firstname.lastname@example.org to schedule a meeting with Meredith after the seminar.
Further information, including the link to add the seminar series to your google calendar, is available from CID Weekly Seminar Series website [http://www.med.monash.edu.au/scs/medicine/cid/seminar-series.html]