The Axis of Tolerance

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Science  28 Mar 2014:
Vol. 343, Issue 6178, pp. 1439-1440
DOI: 10.1126/science.1252785

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The gut poses a unique challenge to the organism. The host must tolerate beneficial commensal bacteria, yet allow for rapid protective responses to invading pathogens. Failure to maintain this balance may cause intestinal disorders such as chronic inflammatory bowel disease. Fortunately, a dynamic, yet robust, state of chronic, low-grade inflammation maintains this balance (“primed homeostasis”). Thus, the host actively engages the gut microbiota, controlling its composition by secreting antimicrobial peptides and immunoglobulins. Conversely, commensals shape the gut-associated immune system by controlling the prevalence of distinct T cell populations (1). On page 1477 of this issue, Mortha et al. (2) show how communication between specific myeloid and lymphoid cells controls immune homeostasis under exposure to the gut microflora. Such cellular details of this steady state may guide the development of rational therapies for intestinal inflammatory conditions.