Associate Professor Tony Kenna

BSc (Hons), PhD

Principal Research Fellow

About me

Since his undergraduate degree, Dr Tony Kenna has been interested in the complexity of the immune system; the way the human immune systems protects the body from such a wide variety of ‘dangers’, ranging from bacteria and viruses, to parasitic worms and tumours.

His particular interest, however, is the process when the immune system becomes faulty. At its core, autoimmunity is a failure of the immune system to recognise the body’s own cells and tissues as being harmless and instead attacks. The steps that lead the immune system to this ultimately self-destructive stage are hugely complex, but understanding them is critical for the development of therapeutics to treat autoimmune conditions such as arthritis, inflammatory bowel disease, multiple sclerosis and type 1 diabetes.
Dr Tony Kenna undertook his PhD at University College in Dublin, investigating the role of rare populations of T cells in healthy and cancer our liver. Dr Kenna then moved to Queensland and undertook post-doctoral training at The University of Queensland Diamantina Institute, using mouse models of autoimmunity to investigate novel ways to eliminate harmful T cells that cause several autoimmune diseases. Dr Kenna is a current research fellow at UQDI where his work focuses on understanding immune responses in autoimmunity. He is currently supported by an Arthritis Australia Heald Fellowship.
Kenna's current research focuses on understanding the role played by particular immune cell subsets in AS and what triggers inappropriate activation of the immune system in autoimmunity. This has led him down some exciting new pathways, including questioning what role the gut immune system has in autoimmune bone diseases. "We all hear on the TV and radio about healthy digestive systems being important for overall health. One way this is particularly important is in sculpting the immune system." Dr Kenna says, "An unhealthy gut can inappropriately activate the immune system and there’s increasing evidence that such immune system activation can cause autoimmune attack of sites far removed from the gut, including bone."
Dr Kenna’s team focuses primarily on understanding how the immune system contributes to development of a bone disease called ankylosing spondylitis (AS). Work by Professor Matt Brown has identified 33 genes involved in AS. Many of these genes control immune cell function. One of the major research challenges in this field is to understand the biology underlying these genes and how specific immune cells contribute to disease. This knowledge will inform researchers about novel therapeutic targets and strategies that could be trialled in AS.


Immune cell responses in ankylosing spondylitis

In immune-mediated diseases the patient’s immune system is responsible for causing severe damage at targeted sites of the body, be it the brain, joints, gastrointestinal tract or skin. In these conditions, it is expected that the immune cells in the blood, which usually act to clear the body of infections, inappropriately attack the healthy cells of patients leading to the manifestations of the disease.

Blood samples from individuals with the chronic spinal arthritis ankylosing spondylitis (AS) are being used to study the involvement of key genes thought to drive inappropriate immune responses in this disease. Specifically, this project focusses on a group of immune cells called T-cells, and the surface receptors used by these cells to engage with the body’s cells when monitoring for infection. Immunosequencing is a new technique that has been used across the world to look for patterns in T-cell receptor usage by sequencing the genes that encode them. Globally this powerful approach to large-scale sampling of the immune cell population has revelled T-cells associated with immune-diseases, response to infection and anti-tumour immunity. We hope to find T-cell populations that may be targeting inflammatory responses to the sites implicated in AS, the spine, pelvis and gastrointestinal tract.

Investigating transcriptomic and methylomic profiles in immune cell subsets

Ankylosing spondylitis (AS) is the prototypic member of a family of related diseases known as the Spondyloarthritides. Spondyloarthritides also include inflammatory bowel disease (IBD) associated arthritis, psoriatic arthritis and reactive arthritis. The initial stages of AS involves inflammation of the spine and sacroiliac joints of the pelvis, which may then lead to bony ankylosis (fusion of the joint).

Early studies showed that AS is a highly heritable disease, and extensive genetic studies have been carried out on AS cohorts. Currently there are 113 loci associated with AS, many in immune genes including: HLA-B27, components of HLA class I antigen processing, and components of the IL-23immune signalling pathway. These 113 loci account for 27.82% of AS heritability, with HLA-B27 contributing 20.1% of that heritability.

Unfortunately the mechanism through which these loci cause the immune changes that lead to AS is still unknown.

Pairing gene expression (transcriptomics) and methylation (methylomics) information with genotype information can reveal genetic variants that alter gene expression and methylation, known as expression quantitative trait loci (eQTL) and methylation quantitative trait loci (meQTL). Polymorphisms that disrupt DNA motifs that are used by cellular machinery for mRNA production and processing can interfere with the expression of near (cis-) and network associated (trans-) genes.

It is the aim of this project to investigate if genetic changes at these AS associated loci alter gene expression or methylation, either in cis or trans, to elucidate the mechanism through which these genetic changes alter immune function and lead to AS. Unlike past studies, which have investigated expression signals in pooled populations of cells, we are specifically studying immune cell subtypes in isolation to determine genetic variants that act on these specific cells, and isolate cell-type contributions to altered biological processes. A range of immune cells are under scrutiny (CD4+ T-cells, CD8+ T-cells, monocytes, NK cells and gamma-delta T-cells). This will be the largest RNA sequencing and paired methylation project of its kind in AS.


Treating systemic sclerosis in mouse models

Systemic sclerosis (SSc), also known as scleroderma, is a chronic connective tissue condition that is characterised by painful hardening and thickening of the skin, but can also effect a number of internal organs with devastating consequences. Overactivity of the immune system is thought to underly the damage inflicted in those suffering from SSc.

Our group is currently using mouse models of systemic sclerosis (SSc) to investigate the role of inflammatory mediators in disease pathogenesis. These genetic makers are elevated in human scleroderma patients which points toward their importance in the excessive recruitment of inflammatory cells to the skin and unwanted sites of the body. In our group, a small molecule inhibitor of a particular immune-cell binding interaction has been recently shown to prevent disease progression in a mouse model of SSc.


Functional dissection of genetic signals for ankylosing spondylitis

Multiple genome wide association studies have been conducted for the inflammatory spinal arthritis ankylosing spondylitis (AS) since 2007, and thus far at least 113 non-MHC AS associated variants across the genome have been identified as significantly contributing to risk of disease. Despite that, the underlying mechanisms of how genetic differences in AS patients operate to contribute to pathology remains largely unclear. Dissecting the functional consequences of genetic changes associated with AS is a key focus of the group.

The vast majority of AS associated genetic changes lie within non-coding region of the genomes (i.e not in genes that code for protein) and therefore raise a great challenge in unravelling the mechanisms through which they operate. Currently, we use computational approaches that leverage multiple ‘omics data to elucidate causative genes, pathways and critical cell types involved in AS pathogenesis. Recently we applied bioinformatic methods utilising epigenetic, gene transcript and protein expression data to identify the cell types through which AS-associated variants operate. Variants were enriched in transcriptionally regulated regions in monocytes, CD4+ and CD8+ T cells, natural killer cells, regulatory T cells and B cells and mucosa from the small intestine, sigmoid colon and rectum. Gene Ontology term enrichment analysis identified microbes and the gut in the aetiology of AS. These findings identify the key immune cell types that drive the disease, and further highlight the involvement of the gut microbiome in the pathogenesis of AS.



1. T.J. Kenna, S.I. Davidson, R. Duan, L. Bradbury, J. McFarlane, M. Smith, H. Weedon, S. Street, R. Thomas, G.P. Thomas and M.A. Brown. Enrichment of circulating IL-17-secreting IL-23 receptor-positive γδ T cells in patients with active ankylosing spondylitis. Arthritis and Rheumatism, EPub Dec 5 2011
2. T.J. Kenna, S.I. Davidson, G.P. Thomas. The genomics and genetics of ankylosing spondylitis. In press, Advances in Genomics and Genetics, EPub Dec 2011
3. The Australo-Anglo-American Spondyloarthritis Consortium (TASC); the Wellcome Trust Case Control Consortium 2 (WTCCC2), Evans DM, Spencer CC, Pointon JJ, Su Z, Harvey D, Kochan G, Opperman U, Dilthey A, Pirinen M, Stone MA, Appleton L, Moutsianis L, Leslie S, Wordsworth T, Kenna TJ, Karaderi T, Thomas GP, Ward MM, Weisman MH, Farrar C, Bradbury LA, Danoy P, Inman RD, Maksymowych W, Gladman D, Rahman P; Spondyloarthritis Research Consortium of Canada (SPARCC), Morgan A, Marzo-Ortega H, Bowness P, Gaffney K, Gaston JS, Smith M, Bruges-Armas J, Couto AR, Sorrentino R, Paladini F, Ferreira MA, Xu H, Liu Y, Jiang L, Lopez-Larrea C, Díaz-Peña R, López-Vázquez A, Zayats T, Band G, Bellenguez C, Blackburn H, Blackwell JM, Bramon E, Bumpstead SJ, Casas JP, Corvin A, Craddock N, Deloukas P, Dronov S, Duncanson A, Edkins S, Freeman C, Gillman M, Gray E, Gwilliam R, Hammond N, Hunt SE, Jankowski J, Jayakumar A, Langford C, Liddle J, Markus HS, Mathew CG, McCann OT, McCarthy MI, Palmer CN, Peltonen L, Plomin R, Potter SC, Rautanen A, Ravindrarajah R, Ricketts M, Samani N, Sawcer SJ, Strange A, Trembath RC, Viswanathan AC, Waller M, Weston P, Whittaker P, Widaa S, Wood NW, McVean G, Reveille JD, Wordsworth BP, Brown MA, Donnelly P. Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nat Genet. 2011 Jul 10. doi: 10.1038/ng.873
4. E.A. Glazov, A. Zankl, M. Donskoi, T.J. Kenna, G.P. Thomas, G.R. Clark, E.L. Duncan, M.A. Brown. Whole-exome re-sequencing in a family quartet identifies POP1 mutations as the cause of a novel skeletal dysplasia. PLoS Genet 7(3): e1002027. 2011
5. J.K. Broom, A.M. Lew, H. Azukizawa, T.J. Kenna, G.R. Leggatt, I.H. Frazer. Antigen-specific CD4 cells assist CD8 T-effector cells in eliminating keratinocytes. J Invest Dermatol. 2010 Feb 11.
6. T.J. Kenna, T. Waldie, A. McNally, M. Thomson, H. Yagita, R. Thomas, R.J.Steptoe. Targeting antigen to diverse antigen-presenting cells inactivates memory CD8+ T-cells without eliciting tissue-destructive effector function. J Immunol. 15;184(2):598-606. 2010
7. T.J. Kenna, R. Thomas, R.J. Steptoe. Steady state dendritic cells expressing cognate antigen terminate memory CD8+ T cell responses. Blood 111 (4): 2091-100. 2008
8. T. Kenna, M. O’Brien, A.E. Hogan, M.A. Exley, S.A. Porcelli, J.E. Hegarty, C. O’Farrelly, D.G.Doherty. CD1 expression and CD1-restricted T cell activity in normal and tumour-bearing human liver. Cancer Immunol Immunother, 56(4): 563-72.
9. T. Kenna, L. Golden-Mason, S. N. Norris, G. McEntee, O. Traynor, J. E. Hegarty, Cliona O’Farrelly, D. G. Doherty. Distinct subpopulations of gd T cells are present in normal and tumor-bearing human liver. Clin Immunol 113 (1): 56-63. 2004
10. T. Kenna, L. Golden Mason, S. A. Porcelli, Y. Koezuka, J. E. Hegarty, C. O’Farrelly, D. G. Doherty. Natural killer T (NKT) cells from normal and tumor-bearing human livers are phenotypically and functionally distinct from murine NKT cells. J Immunol 171: 1775-1779. 2003.

Research fields

Inflammatory arthritis, autoimmunity, immunology