The vertebrate immune system develops in layers, as modes of immunity have evolved on top of each other through time with the expansion of organismal complexity. The maturation timing of immune cell subsets, such as innate immune cells, innate-like cells and adaptive cells, corresponds to their physiological roles in protective immunity. While various cell subsets have specialized roles, they also complement each other to clear pathogens, resolve inflammation and maintain homeostasis, especially at barrier sites with high microbial density. Immune cells adapt to inflammatory insults through mechanisms including epigenetic and metabolic reprogramming, clonal expansion and enhanced communication with the surrounding tissue environment. Over time, these adaptations shape an individual immune identity, reflective of the overlay between the genetic predisposition and the antigenic and environmental exposures of each individual. While some aspects of this immune shaping are natural consequences of immune maturation over time, others are maladaptive and predispose to irreversible pathology. In this Perspective, we provide a framework for categorizing the shaping events of the immune response, in terms of mechanisms, contexts and functional outcomes. We aim to clarify how these terms can be appropriately applied to future findings that impact immune function.
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We would like to thank B. McDonald and D. Sharma for careful review of this manuscript and the many related discussions that helped strengthen the key points. We thank D. Mucida and M. Constantinides for helpful discussions that enhanced our understanding of neuro–immune axis perturbations and MAIT cells, respectively. This work was supported by the National Institutes of Health R01DK067180 (to B. J.), R01DK098435 (to B. J.), R01DK063158 (to B. J.), R01DK126487 (to B. J.) and the Digestive Diseases Research Core Center P30 C-IID DK42086 (to B. J.) at the University of Chicago, the 2019PG-CD015 Helmsley Charitable trust grant (to B. J), 5T32DK007074-49 (to A. H.-S.), Duchossois Family Institute (DFI) Fellowship Grant (to A. H.-S.), and the Gastro-Intestinal Research Foundation (GIRF) Pilot Award Grant (to A. H.-S).
The authors declare no competing interests.
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Halper-Stromberg, A., Jabri, B. Maladaptive consequences of inflammatory events shape individual immune identity. Nat Immunol 23, 1675–1686 (2022). https://doi.org/10.1038/s41590-022-01342-8