The trillions of microbial symbionts normally hosted by mammals have important influences on the development and function of the immune system. We highlight recently discovered cellular and molecular mechanisms by which they impact autoimmune diseases-in particular, gut-distal disorders. Besides provoking a reconsideration of the definition of immunological self and nonself, these new findings evoke exciting possibilities for the discovery of a whole new class of immunomodulatory molecules.
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