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Inflammatory memory and tissue adaptation in sickness and in health

Abstract

Our body has a remarkable ability to remember its past encounters with allergens, pathogens, wounds and irritants, and to react more quickly to the next experience. This accentuated sensitivity also helps us to cope with new threats. Despite maintaining a state of readiness and broadened resistance to subsequent pathogens, memories can also be maladaptive, leading to chronic inflammatory disorders and cancers. With the ever-increasing emergence of new pathogens, allergens and pollutants in our world, the urgency to unravel the molecular underpinnings of these phenomena has risen to new heights. Here we reflect on how the field of inflammatory memory has evolved, since 2007, when researchers realized that non-specific memory is contained in the nucleus and propagated at the epigenetic level. We review the flurry of recent discoveries revealing that memory is not just a privilege of the immune system but also extends to epithelia of the skin, lung, intestine and pancreas, and to neurons. Although still unfolding, epigenetic memories of inflammation have now been linked to possible brain disorders such as Alzheimer disease, and to an elevated risk of cancer. In this Review, we consider the consequences—good and bad—of these epigenetic memories and their implications for human health and disease.

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Fig. 1: Overview of inflammatory and tissue memory.
Fig. 2: Mechanisms of memory.

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Acknowledgements

We thank our many friends and colleagues who have made this field such an exciting and important one; A. Gola, M. Parigi, S. Larsen, C. Cowley, R. Niec, S. Sajjath, D. Rosenblum, P. Konieczny and L. Gueinin-Mace for their helpful comments on our manuscript. Illustrations were generated using Biorender. E.F. is an HHMI Investigator funded by grants from the US National Institutes of Health (R01-AR27883, R01-AR31737 and R01-AR050452). S.N. is a NYSCF Robertson Stem Cell Investigator and is funded by grants from the US National Institutes of Health (1DP2AR079173-01 and R01-AI168462), the Pew Foundation (00034119) and the Packard Foundation.

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S.N and E.F. conceptualized and compiled the manuscript and illustrations.

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Correspondence to Shruti Naik or Elaine Fuchs.

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S.N. is on the scientific advisory board of Seed Inc., is a consultant for BiomX and receives research funding from Takeda Pharmaceuticals. E.F. has recently served on the scientific advisory boards of L’Oreal and Arsenal Biosciences, and owns stock options for Arsenal Biosciences.

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Naik, S., Fuchs, E. Inflammatory memory and tissue adaptation in sickness and in health. Nature 607, 249–255 (2022). https://doi.org/10.1038/s41586-022-04919-3

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