Functional Contributions of Antigen Presenting Cells in Chronic Graft-Versus-Host Disease

Abstract

Chronic graft-versus-host disease (cGVHD) is one of the most common reasons of late non-relapse morbidity and mortality of patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). While acute GVHD is considered driven by a pathogenic T cell dominant mechanism, the pathogenesis of cGVHD is much complicated and involves participation of a variety of immune cells other than pathogenic T cells. Existing studies have revealed that antigen presenting cells (APCs) play crucial roles in the pathophysiology of cGVHD. APCs could not only present auto- and alloantigens to prime and activate pathogenic T cells, but also directly mediate the pathogenesis of cGVHD via multiple mechanisms including infiltration into tissues/organs, production of inflammatory cytokines as well as auto- and alloantibodies. The studies of this field have led to several therapies targeting different APCs with promising results. This review will focus on the important roles of APCs and their contributions in the pathophysiology of cGVHD after allo-HSCT.

Immunohistopathology of oral mucosal chronic graft‐versus‐host disease severity and duration

“…However, an increasing trend was seen with clinical and histopathological severity and time post-HCT, as om-cGVHD (GII) was significantly reduced at onset, whereas mild and severe (GIII-GIV) were NS compared with healthy volunteers. These data could support a role in priming the cytotoxic cGVHD response (Hong, Jin, Dai, & Gao, 2021).…”

“…APC levels diminish and quickly undergo donor chimerism; hence, APC reconstitution remains to be fully ascertained within the first year (Aractingi et al, 1997;Hong et al, 2021).…”

Neutrophils as regulators of macrophage-induced inflammation in a setting of allogeneic bone marrow transplantation

“…In addition, the use of a mouse BMT model with a myeloablative preparative regimen excluded the possibility of investigating the functions of other host-derived myeloid cells, such as macrophages, in post-BMT sepsis. Since host-derived macrophages could play distinct roles versus donor-derived macrophages in GVHD ( Hashimoto et al., 2011 ; Jardine et al., 2020 ; Hong et al., 2021 ), their functions in immune regulation and inflammation post-BMT will merit further investigation in different mouse BMT models.…”

Gene expression profile of chronic oral graft-versus-host disease

“…It involves mixed infiltrating inflammatory cells and the production of allo-and auto-antibodies by aberrant B cells that exacerbate direct or indirect inflammatory responses [2,3]. A defective immune tolerance in the hosts after allo-HSCT might also favor progress and the occurrence of chronic GVHD [4].…”