Mucus Enhances Gut Homeostasis and Oral Tolerance by Delivering Immunoregulatory Signals

Guardian of the Gut The intestine is able to tolerate continual exposure to large amounts of commensal bacteria and foreign food antigens without triggering an inappropriate inflammatory immune response. In the large intestine, this immunological tolerance is thought to occur via a physical separation between environment and host imposed by a continuous mucous layer built up from the secreted mucin protein, MUC2. However, in the small intestine, this mucous layer is porous, necessitating an additional layer of immune control. Shan et al. (p. 447 , published online 26 September; see the Perspective by Belkaid and Grainger ) now report that in the small intestine, MUC2 plays an active role in immunological tolerance by activating a transcription factor in resident dendritic cells, thereby selectively blocking their ability to launch an inflammatory response. This work identifies MUC2 as a central mediator of immune tolerance to maintain homeostasis in the gut and possibly at other mucosal surfaces in the body.