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The Interplay between Innate Immune Memory and Adaptive Immunity: Emerging Mechanisms in Alloimmunity.

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

Authors: Maaike Jacobs, Lisanne C de Jong, Nils Rother, Luuk B Hilbrands, Leo A B Joosten, Willem J M Mulder, Mihai G Netea, Raphaël Duivenvoorden

Innate immune memory is increasingly recognized as a regulator of immune responses in solid organ transplantation. Following an initial stimulus, innate immune cells and their progenitors can undergo epigenetic and metabolic reprogramming, resulting in enhanced or suppressed pro-inflammatory responses upon subsequent encounters, termed trained immunity and innate immune tolerance, respectively. These antigen-independent forms of innate immune memory are complemented by donor-specific innate immune memory. Importantly, innate immune memory may influence alloimmune responses by shaping adaptive T cell activation through altered cytokine production, antigen presentation, and co-stimulatory signals. Conversely, adaptive immune cells can regulate the induction of innate immune memory, highlighting a bidirectional innate-adaptive crosstalk. In this review, we discuss the interplay of innate immune memory with adaptive immunity, and the potential to harness this mechanism to promote graft survival and long-term tolerance.

Copyright © 2026 The Author(s). Published by Elsevier Inc. All rights reserved.

PMID: 42705464

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