The emergence of the adaptive immune system in vertebrates set the stage for evolution of an advanced symbiotic relationship with the intestinal microbiota. The defining features of specificity and memory that characterize adaptive immunity have afforded vertebrates the mechanisms for efficiently tailoring immune responses to diverse types of microbes, whether to promote mutualism or host defence. These same attributes can put the host at risk of immune-mediated diseases that are increasingly linked to the intestinal microbiota. Understanding how the adaptive immune system copes with the remarkable number and diversity of microbes that colonize the digestive tract, and how the system integrates with more primitive innate immune mechanisms to maintain immune homeostasis, holds considerable promise for new approaches to modulate immune networks to treat and prevent disease.
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The authors thank D. Randolph and C. Morrow for discussions and critical review of this manuscript. C.T.W., C.O.E. and R.D.H. are supported by grants from the National Institutes of Health, and C.T.W. and C.L.M. are supported by grants from the Crohn's and Colitis Foundation of America. The authors extend their apologies to colleagues whose work could not be adequately acknowledged owing to space limitations.
The authors declare no competing financial interests.
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Maynard, C., Elson, C., Hatton, R. et al. Reciprocal interactions of the intestinal microbiota and immune system. Nature 489, 231–241 (2012). https://doi.org/10.1038/nature11551
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