DNA amplification moves on

whether fasting and changes in diet might be changing leptin levels, thus altering the function of T cells. The implication of this new work is that leptin drives the activity of pro-inflammatory, self-reactive T cells, and that starvation, which reduces leptin production, changes the pattern of cytokines generated and the disease-inducing potential of the T cells. So, the authors show that instead of producing pro-inflammatory cytokines, T cells from the starved mice generate anti-inflammatory cytokines, which generally inhibit and regulate organ-specific autoimmune diseases. The idea that leptin could also have a significant role in multiple sclerosis is strengthened by studies of the genes expressed in the brains of patients with this disease: leptin and related genes are expressed more than usual. In the context of the whole animal, however, there is still much to understand about the potential interactions between fat metabolism and immunity. The importance of these questions to multiple sclerosis is highlighted by another recent study of EAE. This work found that drugs of the statin family, which inhibit the enzyme 3-hydroxy3-methylglutaryl coenzyme A reductase and reduce cholesterol levels, are also beneficial to animals with EAE, again by altering the cytokine profile of self-reactive T cells. Another enzyme — stearoyl coenzyme A desaturase-1, which is involved in fatty-acid synthesis — is thought to contribute to leptin’s effects on metabolism. Although these enzymes are on different biosynthetic pathways, their genes are regulated by a common set of gene-transcription factors (adipocyte-determination differentiation-dependent factors, also called sterolregulatory-element-binding proteins) that also regulate the leptin gene. So the coordinated control of these different metabolic pathways and leptin could be tied, by transcription factors, both to each other and to aspects of immune function. In a broader context, these results illustrate once again the trade-off between resistance to infection and susceptibility to autoimmunity. This view is supported by genetic evidence that the regions on chromosomes that influence susceptibility to infection overlap with those that influence susceptibility to autoimmune disease. The demonstration that starvation can stop EAE reminds us how profoundly our state of immunity is also contingent on our relationship with the environment. Adequate nutrition supports an immune response poised to repulse pathogens. It may also be the best substrate for the seed of autoimmunity to take root. ■