Innate allorecognition by monocytic cells and its role in graft rejection

Abstract

Innate recognition of microbial products and danger molecules by monocytes and macrophages has been well established; this is mediated primarily by pattern-recognition receptors and is central to the activation of innate and adaptive immune cells required for productive immunity. Whether monocytes and macrophages are equipped with an allorecognition system that allows them to respond directly to allogeneic grafts is a topic of much debate. Recent studies provide compelling evidence that these cells can recognize allogeneic entities and that they mediate graft rejection via direct cytotoxicity and priming of alloreactive T cells. In addition, these studies have uncovered a mechanism of innate allorecognition based on detection of the polymorphic molecule signal regulatory protein α (SIRPα) on donor cells. Further understanding of innate allorecognition and its consequences would provide essential insight into allograft rejection and lead to better therapies for transplant patients.

Inhibiting Inflammation with Myeloid Cell-Specific Nanobiologics Promotes Organ Transplant Acceptance

“…This therapeutic approach enables targeting graft infiltrating myeloid cells, whose role in initiating and sustaining graft-reactive immune response has recently become apparent (Zhuang et al, 2016). The focused in vivo delivery not only ‘redirects’ rapamycin to myeloid cells, but also has the potential to limit its associated side effects, such as impaired wound healing (Lakkis and Li, 2018).…”

Landscape of innate immune system transcriptome and acute T cell–mediated rejection of human kidney allografts

“…In animal models, skin and cardiac allografts without evidence of inflammation are vigorously rejected by transferred T cells or when recipients are reconstituted with T cells at a physiologic rate by nude bone graft transplantation (76). In contrast, emerging studies in animal models have provided compelling evidence that innate cells engage in allorecognition and this form of nonmicrobial, nonself-recognition, referred to as innate allorecognition, plays an important role in rejection (77).…”

Germinal center humoral autoimmunity independently mediates progression of allograft vasculopathy

“…A possible alternative is that allograft damage is initiated by innate immune recognition of nonself alloantigen. This is a recently described concept, and remains poorly understood [47], but it is now evident that monocytes [48] and NK cells [49] , can respond to allogeneic determinants, such as the recently-described polymorphisms in signal regulatory protein α [SRPα [50]].…”