Scientists working at the MRC National Institute for Medical Research have shown that environmental factors can influence the development of autoimmune diseases like multiple sclerosis.
A team led by Dr Brigitta Stockinger has identified a molecular mechanism that links a wide range of environmental factors to the autoimmune reactions in which immune system cells attack body tissue. The results are published online in Nature.
The research focused on a protein called the aryl hydrocarbon receptor (AhR). Activation of the AhR causes enzymes to be produced that are involved in reducing the toxic effect of a wide range of chemicals on the human body. Many of these, such as dioxin, are generated in industrial processes. The research found that stimulation of AhR by environmental factors could be involved in development of autoimmune disease.
The researchers looked at the effect that both AhR and environmental factors had on autoimmune disease in mice.Dr Stockinger said: ‘‘Multiple factors can influence the development of autoimmune diseases, these include genetics, hormones, diet, the presence of infection or exposure to chemical and environmental irritants. Autoimmune diseases are becoming increasingly common in industrialised countries and it is likely that this is connected to environmental factors.''
The AhR is present in a group of T helper cells called Th17 in both the mouse and human immune systems. T helper cells generate a response to infection by stimulating the immune cells that produce antibodies and those that destroy other infected cells.
Under normal circumstances, Th17 cells are important in mounting an immune reaction to fungal and bacterial infection. Th17 cell activity is also the cause of some autoimmune diseases including multiple sclerosis and rheumatoid arthritis.
The research found that if AhR is activated in mice while Th17 cells are developing, the proportion of Th17 cells present in the body increases and so the potential for the development of autoimmune disease is enhanced. The AhR is activated by environmental factors.Dr Stockinger explains: ‘‘The AhR system can potentially react to an astounding range of factors, from environmental pollutants to particular foods or even hormone levels. So here we have identified a molecular mechanism that shows how such a wide range of environmental factors could be directly linked to the cells that cause autoimmune reactions.''
In comparison, mice that lack AhR still develop Th17 cells and T helper cell responses but they don't have enhanced numbers of these cells. This suggests that AhR interaction with environmental factors leads to an increase in the number of Th17 cells and may contribute to the onset or development of autoimmune diseases in genetically susceptible individuals. In addition, the research showed that stimulation of AhR resulted in faster development of autoimmunity with greater severity. This means that environmental factors are interacting with genetic factors to generate a detrimental autoimmune reaction.
Dr Stockinger concludes: ‘‘The discovery that the stimulation of AhR by environmental pollutants can accelerate the development of autoimmune reactions and the severity of symptoms raises intriguing possibilities and warrants closer examination of a possible role of AhR in human autoimmune diseases."