University of Dundee

Dr Simon Arthur

Signaling networks that control inflammation
Reader and Deputy Head of the Division of Cell Signalling and Immunology
College of Life Sciences, Sir James Black Centre, University of Dundee, Dundee DD1 5EH
Full Telephone: 
+44 (0) 1382 384003, int ext 84003


The body's immune system is essential for defense against infection and wound healing. However excessive, or inappropriate, activation of the immune system results in unwanted damage to healthy tissue. Infection or injury is detected by immune cells, which then trigger a complex inflammatory reaction designed to clear the pathogen and/or promote tissue repair. Normally this is then followed by a resolution phase during which inflammation decreases and the immune system is deactivated. Excessive inflammation however can cause tissue damage or cytokine storms. In severe cases this can result in septic shock, a condition that still has limited treatment options and high mortality. A failure of resolution results in chronic inflammation, a condition that underlies the pathology of autoimmune and auto-inflammatory conditions. These diseases, which include rheumatoid arthritis, psoriasis, lupus and vasculitis, represent a major health problem, and together can affect 3-4% of the population in Western society. Autoimmune disorders are often serious and can lead to significant disability and in some cases mortality. While modern drug treatments can be effective in providing relief from these conditions, they do not provide a cure and can themselves result in significant adverse side effects. Thus more research is needed to provide a full understanding of the causes and pathology of these conditions to enable improved therapies to be developed. Inflammation is a complex multistage process involving multiple cell types from both the innate and adaptive immune systems and is tightly coordinated by a range of pro-inflammatory cytokines and chemokines. Further control is also achieved via the induction of anti-inflammatory cytokines that act to keep inflammation within acceptable limits and to promote the resolution of inflammation.

We are primarily interested in the roles that cells of the innate immune system play in coordinating inflammation and how they contribute to activation of adaptive immunity via the production of cytokines. Innate immune cells are able to recognize specific components of pathogens – referred to as pathogen associated molecular patterns or PAMPs. Several groups of receptors for PAMPs have been described, including Toll like receptors, C-type lectins and NOD-like proteins. These receptors trigger the activation of several intracellular signaling pathways, including the mitogen activated protein kinase (MAPK), NFkappaB and TBK1/IRF systems leading to the transcription and production of both pro- and anti-inflammatory cytokines. Our main focus is to understand the roles these intracellular signaling cascades play in both the initial inflammatory response and in the ability of innate immune cells, particularly macrophages and dendritic cells, to activate the adaptive immune system. Finally we are interested in the ways in which intracellular signaling in innate immune cells controls the induction of anti-inflammatory and pro-resolution factors in order to deactivate the immune system.


BS31006 - Genetics

BS32006 - Cell Signalling

BS32009 - Immunology

BS42006 - Advanced Immunology

BS42013 - Advanced Cell Signalling


  1. Zhou, Z., Tang, A. T., Wong, W. Y., Bamezai, S., Goddard, L. M., Shenkar, R., Zhou, S., Yang, J., Wright, A. C., Foley, M., Arthur, J. S., Whitehead, K. J., Awad, I. A., Li, D. Y., Zheng, X. and Kahn, M. L. (2016) Cerebral cavernous malformations arise from endothelial gain of MEKK3-KLF2/4 signalling. Nature. 532, 122-126
  2. Tan, L., Akahane, K., McNally, R., Reyskens, K. M., Ficarro, S. B., Liu, S., Herter-Sprie, G. S., Koyama, S., Pattison, M. J., Labella, K., Johannessen, L., Akbay, E. A., Wong, K. K., Frank, D. A., Marto, J. A., Look, T. A., Arthur, J. S., Eck, M. J. and Gray, N. S. (2015) Development of Selective Covalent Janus Kinase 3 Inhibitors. J Med Chem. 58, 6589-6606
  3. Naqvi, S., Martin, K. J. and Arthur, J. S. (2014) CREB phosphorylation at Ser133 regulates transcription via distinct mechanisms downstream of cAMP and MAPK signalling. Biochem J. 458, 469-479
  4. McGuire, V. A., Gray, A., Monk, C. E., Santos, S. G., Lee, K., Aubareda, A., Crowe, J., Ronkina, N., Schwermann, J., Batty, I. H., Leslie, N. R., Dean, J. L., O'Keefe, S. J., Boothby, M., Gaestel, M. and Arthur, J. S. (2013) Cross talk between the Akt and p38alpha pathways in macrophages downstream of Toll-like receptor signaling. Mol Cell Biol. 33, 4152-4165
  5. Arthur, J. S. and Ley, S. C. (2013) Mitogen-activated protein kinases in innate immunity. Nat Rev Immunol. 13, 679-692
  6. Venigalla, R. K., McGuire, V. A., Clarke, R., Patterson-Kane, J. C., Najafov, A., Toth, R., McCarthy, P. C., Simeons, F., Stojanovski, L. and Arthur, J. S. (2013) PDK1 regulates VDJ recombination, cell-cycle exit and survival during B-cell development. EMBO J. 32, 1008-1022
  7. MacKenzie, K. F., Van Den Bosch, M. W., Naqvi, S., Elcombe, S. E., McGuire, V. A., Reith, A. D., Blackshear, P. J., Dean, J. L. and Arthur, J. S. (2013) MSK1 and MSK2 inhibit lipopolysaccharide-induced prostaglandin production via an interleukin-10 feedback loop. Mol Cell Biol. 33, 1456-1467
  8. MacKenzie, K. F., Clark, K., Naqvi, S., McGuire, V. A., Noehren, G., Kristariyanto, Y., van den Bosch, M., Mudaliar, M., McCarthy, P. C., Pattison, M. J., Pedrioli, P. G., Barton, G. J., Toth, R., Prescott, A. and Arthur, J. S. (2013) PGE(2) induces macrophage IL-10 production and a regulatory-like phenotype via a protein kinase A-SIK-CRTC3 pathway. J Immunol. 190, 565-577
  9. Pattison, M. J., Mackenzie, K. F. and Arthur, J. S. (2012) Inhibition of JAKs in macrophages increases lipopolysaccharide-induced cytokine production by blocking IL-10-mediated feedback. J Immunol. 189, 2784-2792
  10. Ananieva, O., Darragh, J., Johansen, C., Carr, J. M., McIlrath, J., Park, J. M., Wingate, A., Monk, C. E., Toth, R., Santos, S. G., Iversen, L. and Arthur, J. S. (2008) The kinases MSK1 and MSK2 act as negative regulators of Toll-like receptor signaling. Nat Immunol. 9, 1028-1036