C–C chemokine receptor 5 and acute graft‐versus‐host disease

• Published in: Immunity, Inflammation and Disease Vol. 10; no. 9; pp. e687 - n/a
• Main Authors: Yuan, Jing, Ren, Han‐yun
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.09.2022; John Wiley and Sons Inc; Wiley
• Subjects: acute graft‐versus‐host disease; Animals; CD8-Positive T-Lymphocytes; Chemokines; Chemokines, CC; C–C chemokine receptor 5; Gene expression; Graft versus host disease; Graft vs Host Disease; HIV; Human immunodeficiency virus; immune mechanism; Inflammation; Ligands; Lymphocytes; Maraviroc - pharmacology; Mice; Pathogenesis; Proteins; Receptors, CCR5 - genetics; Review; Signal transduction; immune mechanism; acute graft-versus-host disease; C-C chemokine receptor 5
• ISSN: 2050-4527; 2050-4527
• DOI: 10.1002/iid3.687

Background The C–C chemokine receptor 5 (CCR5) is mainly expressed in a variety of immune cells. It interacts with multiple chemokine ligands that mediate the trafficking and recruitment of effector cells toward sites of inflammation. CCR5 not only plays a critical role in cell growth, activation, differentiation, adhesion, and migration but also participates in the development of acute graft‐versus‐host disease (GVHD) after allogeneic hematopoietic cell transplantation. Methods This is a literature review article. The research design method is an evidence‐based rapid review. The present discourse aim is first to scrutinize and assess the available literature on CCR5 and acute GVHD. Standard literature and database searches were implemented, gathered relevant material, and extracted information was then assessed. Results CCR5 is a marker of GVHD effector cells, and CCR5 expression is elevated when acute GVHD occurs. CCR5 blockade with maraviroc in clinical trials results in a low incidence of acute GVHD. The immune mechanism includes that CCR5 blockade inhibits donor T cell migration and recruitment toward target organs, reduces the absolute numbers of donor T cells, is capable of slightly suppressing dendritic cell maturation, and reduces the percentage of Th1 and Th17 subsets. CCR5 blockade also inhibits internalization and activation of chemokines, inhibits proliferation and chemotaxis of T cells, and decreases the production of TNF‐α and IFN‐γ. In addition, there may be a form of crosstalk between CCR5 and CCR2. Inconsistently, infusion of CCR5−/− Tregs into lethally irradiated mice significantly increased the infiltration of CD4+ and CD8+ T cells into the liver, resulting in earlier and more severe GVHD. Conclusion This review indicates that CCR5 plays an important role in pathogenesis and development of acute GVHD. Elucidating its role in different immune cells will aid the development of targeted therapeutic treatments. Our previous studies demonstrate that CCR5 blockade could inhibit donor T cells migration and recruitment toward target organs, reduce the amount of donor T cells in absolute numbers, be capable of slightly suppressing dendritic cells maturation, and reduce the percentage of Th1 and Th17 subsets. CCR5 blockade also inhibits internalization and activation of chemokines, inhibits proliferation and chemotaxis of T cells, and decreases the production of TNF‐α and IFN‐γ. In addition, there may be a form of crosstalk between CCR5 and CCR2.