Innate immunity modulates autoimmunity: Type 1 interferon-b treatment in multiple sclerosis promotes growth and function of regulatory invariant natural killer T cells through dendritic cell maturation

Hypothesis

            In this paper, researchers propose that type 1 interferon-b could be used to suppress autoimmune diseases, specifically type I diabetes and multiple sclerosis, due to its role in the production and function of invariant natural killer cells. Understanding the mechanism of this treatment could lead to it use in many other autoimmune diseases (1).

Aims

            Type 1 interferon-b has been recently used to treat patients who are in remission from multiple sclerosis, and it has been proven to decrease their likelihood of relapse. The goal of this paper is to understand the mechanism by which this occurs by studying the effect of type 1 interferon-b on the invariant natural killer cell / dendritic cell pathway (1). 

            To begin this experiment, monocytes were taken from the peripheral blood of ten patients with different stages of multiple sclerosis. Once the invariant natural killer cells were removed from the monocytes and purified, the levels of cytokines were measured, including IFN-g, IL-10, IL-5, IL-4, and IL-2. All the patients in this experiment were different ages and at various stages of the disease process (1). 

Results

            Type 1 interferon-b not only increases the production of invariant natural killer cells, it also increases their efficacy of cytokine release. All of the patients involved in the trials recorded in this article responded to the treatment and had no relapses for two years. The success of this study was determined by studying the percentages of invariant Va24+ CD3+ natural killer cells before and after the patients were treated with type 1 interferon-b. In all cases, the percentage of these cells in the patients was higher after the treatment when compared to the percentage in the monocytes obtained from the peripheral blood at the beginning of the trial. Controls were used in this trial as well to confirm that the linear increase in invariant natural killer cells was due to the type 1 interferon treatment and not a part of the natural disease process. Although there was an increase in cytokine release, researchers propose that this was an indirect consequence of the administration of the type 1 interferon-b (1). 

Discussion / Summary 

            These results are significant because type 1 interferon-b is crucial in stopping infections by destroying pathogens. These interferons promote the maturation of dendritic cells which increases their capacity to present antigens to T cells and secrete cytokines necessary to fight infections. This study proved that type 1 interferon-b has the ability to inhibit autoreactive T cells while also promoting the proliferation and function of regulatory T cells. The mechanism by which type 1 interferon-b acts is through promoting the maturation of dendritic cells. When dendritic cells mature, they activate regulatory T cells and promote the release of costimulatory molecules. By understanding the mechanism by which this occurs, researchers now have a foundation for other autoimmune disorder treatments such as rheumatoid arthritis. Because of the conclusions of this study, researchers in the future will be able to develop treatments for many other autoimmune diseases that are T cell mediated (1). 

References

1. Gigli, G., Caielli, S., Cutuli, D., & Falcone, M. (2007). Innate immunity modulates autoimmunity: type 1 interferon-b treatment in multiple sclerosis promotes growth and function of regulatory invariant natural killer T cells through dendritic cell maturation. Immunology, 122. 409-417. doi:10.1111/j.1365-2567.2007.02655.x