PIRs mediate innate myeloid cell memory to nonself MHC molecules

TLDR

Innate immune cells can exhibit memory‑like responses, a phenomenon previously thought to be exclusive to B and T cells. The study investigates whether myeloid cells can develop antigen‑specific memory through PIR‑As, offering new targets to improve transplant outcomes. Monocytes and macrophages acquire MHC I‑specific memory via PIR‑As, driving allograft rejection, and blocking PIR‑As in mice reduces kidney and heart transplant rejection. Science, this issue p.

Abstract

Innate immune cells remember Immunological memory is a phenomenon by which immune cells can quickly recognize an antigen that the host has previously encountered. Certain cells of the innate immune system exhibit memory-like responses know as trained immunity. Rapid, antigen-specific secondary (anamnestic) responses were long thought to be the domain of B and T cells. However, Dai et al. report that monocytes and macrophages can acquire memory specific for particular major histocompatibility complex I antigens using paired A-type immunoglobulin-like receptors (PIR-As) (see the Perspective by Dominguez-Andrés and Netea). This pathway contributes to recognition and rejection of allograft-transplanted tissue from a donor of the same species. Genetic depletion or blockade of PIR-As in mice diminished the rejection of kidney and heart allografts. This work, which expands immunological memory to include myeloid cells, points to targets that may improve organ transplantation outcomes in the future. Science , this issue p. 1122 ; see also p. 1052