Developing new therapies for Systemic Lupus Erythematosus
Professor Mackay's laboratory has an interest in autoimmune diseases and mechanisms leading to loss of immune tolerance, in particular that of B-lymphocytes. Systemic Lupus Erythematosus (SLE) is a debilitating autoimmune disease driven by aberrant B cells producing antibodies against self. This leads to inflammation and ultimately tissue destruction. Today we have no cure for SLE and the current treatments are symptom-focussed. Attempts to treat lupus by targeting B cells come at the high price of immunosuppression and opportunistic infections. Therefore, a more targeted approach is needed.
Our lab has shown that the molecules BAFF and its receptor TACI play a vital role in autoimmune diseases. Excess BAFF leads to autoimmunity in mice and is also associated with human autoimmunity, in particular Systemic Lupus Erythematosus (SLE) and Sjögren's syndrome. We have demonstrated that TACI-mediated production of autoantibodies is key to drive BAFF-mediated autoimmunity and that loss of TACI on B cells protects from the disease without compromising B cell adaptive immunity in general. We are currently developing strategies targeting TACI to provide a therapy with a higher safety profile that avoids the serious adverse effects of global B cell depletion.
Concurrently, we also investigate the effects of dietary changes on the development and treatment of autoimmune conditions like SLE as we have recently found that a high fibre diet has the potential to reverse disease and reduce pre-established auto-antibodies. Using various approaches we investigate how changes in metabolites and gut microbiota lead to the re-programming of immune responses in the SLE model.
Professor Fabienne MAckay, Lab Head
Dr William Figgett, Postdoctoral Researcher
Professor Chris Goodnow, Garvan Institute, Sydney
Professor Carola Vinuesa, John Curtins School, ANU, Canberra
Dr Stuart Tangye, Garvan Institute, Sydney
Dr Robert Brink, Garvan Institute, Sydney
Dr Matthew Cook, John Curtins School, ANU, Canberra
Dr Ansem Enders, John Curtins School, ANU, Canberra
Dr Jon Sprent, Garvan Institute, Sydney
NHMRC Grant: Molecular and cellular basis of inflammatory and immunodeficiency diseases - 2012-2016
NHMRC Development Grant: Development of a safer new treatment for systemic lupus erythematosus that preserves B cell immunity - 2016-2019
- Mackay F, Schneider P. Cracking the BAFF code. Nat Rev Immunol 2009; 9: 491-502
- Fairfax KA, Tsantikos E, Figgett WA, Vincent FB, Quah PS, LePage M, Hibbs ML, Mackay F. BAFF-driven autoimmunity requires CD19 expression. J Autoimmun 2015; Aug 62: 1-10.
- Figgett WA, Deliyanti D, Fairfax KA, Quah PS, Wilkinson-Berka JL, Mackay F. Deleting the BAFF receptor TACI protects against systemic lupus erythematosus without extensive reduction of B cell numbers. J Autoimmun 2015; Jul 61: 9-16.
- Figgett WA, Vincent FB, Saulep-Easton D, Mackay F. Roles of ligands from the TNF superfamily in B cell development, function, and regulation. Semin Immunol 2014; Jun 26(3): 191-202.
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