Mark Travis, BSc PhD
Integrin immunobiology

The immune system functions to detect and destroy harmful pathogens that enter the body. Upon infection, the immune system is rapidly activated, to ensure the threat is dealt with as quickly as possible. Failure to efficiently activate the immune system to deal with infections can lead to disorders such as overwhelming or chronic infection. However, in healthy individuals it is vital that the immune system is kept in a resting state to prevent tissues of the body from being attacked. If the immune system is activated inappropriately, our own organs and tissues can be attacked resulting in debilitating autoimmune diseases such as inflammatory bowel disease, diabetes and multiple sclerosis.

Certain integrins can bind to and activate latent TGF-betaResearch carried out in our laboratory aims to increase our understanding of the pathways, cells and molecules that control the balance between a resting and active immune system, and how changes in these processes can lead to devastating immune-related diseases. Our research is currently focussed on an important molecule in the immune system called transforming growth factor-b (TGF-β). We are interested in how this molecule controls different types of immune response in the body, especially in the intestine, and how TGF-β itself is regulated to control the immune system. Our work therefore aims to provide important biological insights into how we successfully deal with infection, and how the immune system is tightly regulated to prevent autoimmune disease.

The scientific story

The immune system has evolved to protect the body from harmful pathogens. To function properly, the immune system must be tightly regulated so that it is switched on/off only at appropriate times and in appropriate locations in the body. When this regulation is compromised, disease situations can arise- for example, overwhelming infection if the immune system is not activated appropriately in response to pathogens, or autoimmune disease (e.g. inflammatory bowel disease, diabetes, arthritis) if the immune system is not prevented from attacking self-tissues. Therefore, understanding the factors and pathways that are important in regulation of the immune system will be important in understanding pathologies caused by aberrant immune responses.

Severe inflammation in the intestine occurs when specific pathways of TGF-beta activation are disruptedOur current work focuses on a key extracellular matrix molecule involved in regulating the immune system: the anti-inflammatory cytokine transforming growth factor-b (TGF-β). TGF-β is secreted from cells in an inactive form that needs to be activated to exert effects on TGF-β receptor-expressing cells. We have recently identified the integrin receptor, αvβ8, as an important activator of TGF-β in the immune system. Disruption of this pathway results in a loss of immune homeostasis, resulting in self-harmful immune responses.

Our current research focuses on understanding the mechanisms and important biological outcomes of integrin-mediated TGF-β activation in the immune system. Specifically, how is integrin-mediated TGF-β activation controlled? How does this process affect other immune cell types in order to mediate its function? What other biological outcomes are controlled by integrin-mediated TGF-β activation? Answering these questions will provide important insights into how TGF-β functions, and the pathways by which TGF-β tightly regulates immune responses.

Recent discoveries:

Putting out the flames of inflammation

Recent key publications

Worthington, J.J., Kelly, A., Smedley, C., Bauché, D., Campbell, S., Marie, J.C. and Travis, M.A. (2015). Integrin αvβ8-mediated TGFβ activation by effector regulatory T-cells is essential for suppression of T-cell-mediated inflammation. Immunity. 42, 903-915. PubMed

Travis MA, Sheppard D. (2014). TGF-β Activation and Function in Immunity. Annu Rev Immunol. 32, 51-82. PubMed

Worthington, J.J., Klementowicz, J.E., Rahman, S., Czajkowska, B.I., Smedley, C., Waldmann, H., Sparwasser, T., Grencis, R.K. and Travis, M.A. (2013). Loss of the TGFβ-activating integrin αvβ8 on dendritic cells protects mice from chronic intestinal parasitic infection via control of type 2 immunity. PLoS Pathogens, 9, e1003675. PubMed

Full list of publications