Lead Researcher:
Associate Professor Michael Grimm, Dr Greta Lee, Dr Watson Ng, Ms Annie Luo, Professor Andrew Lloyd, Prof Hazel Mitchell, Dr Andrew Day
Significance
Crohn’s disease and ulcerative colitis are inflammatory diseases of the gut that result in chronic diarrhoea, intestinal bleeding, abdominal pain and, in some, severe debilitation. Their prevalence is increasing markedly and they now affect approximately 310 per 100000 of the population, mostly in younger age groups. Access Economics have estimated the annual cost to the Australian community at $2.7 billion. Despite this, they are hidden conditions, which are rarely discussed. The mechanisms by which these diseases arise and are perpetuated are poorly understood, but the complex gut immune system and its interactions with intestinal microbes are critical and the subject of our research.
Major achievements
We have demonstrated that our gut immune and hormonal systems produce proteins such as endorphins that are specifically able to render our immune cells incapable of migrating to sites of infection or inflammation. This also occurs with an externally applied opioid such as morphine, potentially explaining why injecting drug users have reduced ability to fight infection.
We've also been able to explain the phenomenon by which appendicitis can protect patients against the later development of gut inflammation – it does this by generating large numbers of immune-suppressing cells known as regulatory T cells, which migrate from the appendix to the bowel wall. Both of these important findings have improved our understanding of how the gut immune system maintains normal control in the intestine, and how this goes awry in inflammatory bowel diseases.
Current Research
We are exploring in more detail the mechanisms by which appendicitis-induced regulatory T cells can suppress the severe intestinal inflammation that characterises inflammatory bowel diseases, as this may lead to novel approaches to treating these diseases in the future. In addition, we are looking at how a new class of molecules expressed on the surface of immune cells, known as leucocyte immunoglobulin-like receptors, serve to modulate the function of the gut immune system, which has unique features not seen in other immune system sites.
Recent publications
Grimm MC, Ben-Baruch A, Taub DD, Howard OMZ, Resau JH, Wang JM, Ali H, Richardson R, Snyderman R and Oppenheim JJ. Opiates trans-deactivate chemokine receptors: d and m opiate receptor-mediated heterologous desensitization. J Exp Med 1998, 188: 317-325
Grimm MC, Newman R, Hassim Z, Cuan N, Connor SJ, Le Y, Wang JM, Oppenheim JJ and Lloyd AR. Cutting Edge: Vasoactive intestinal peptide acts as a potent suppressor of inflammation in vivo by trans-deactivating chemokine receptors. J Immunol 2003; 171: 4990-4994
Ng WSW, Hampartzoumian T, Lloyd AR, Grimm MC. Appendicitis protects against colitis by induction of IL-10–secreting regulatory CD8+ T cells that migrate to the colon. (Gastroenterology: submitted)
