The chemerin/CMKLR1 axis regulates intestinal graft-versus-host disease

• DOI: 10.1172/jci.insight.154440
• Publication Date: 2023-03-07T19:01:14Z
• Authors: Erica Dander; Paola Vinci; Stefania Vetrano; Camilla Recordati; Rocco Piazza; Grazia Fazio; Donatella Bardelli; Mattia Bugatti; Francesca Sozio; Andrea Piontini; Sonia Bonanomi; Luca Bertola; Elena Tassistro; Maria Grazia Vals...; Stefano Calza; William Vermi; Andrea Biondi; Annalisa Del Prete; Silvano Sozzani; Giovanna D’Amico
• Keywords: Chemerin

Gastrointestinal graft-versus-host disease (GvHD) is a major cause of mortality and morbidity following allogeneic bone marrow transplantation (allo-BMT). Chemerin chemotactic protein that recruits leukocytes to inflamed tissues by interacting with ChemR23/CMKLR1, receptor expressed leukocytes, including macrophages. During acute GvHD, chemerin plasma levels were strongly increased in allo-BM-transplanted mice. The role the chemerin/CMKLR1 axis GvHD was investigated using Cmklr1-KO WT mice transplanted an graft from donors (t-KO) had worse survival more severe GvHD. Histological analysis demonstrated gastrointestinal tract organ mostly affected t-KO colitis characterized massive neutrophil infiltration tissue damage associated bacterial translocation exacerbated inflammation. Similarly, recipient showed intestinal pathology both transplant dextran sulfate sodium-induced colitis. Notably, adoptive transfer monocytes into mitigated manifestations decreasing gut inflammation T cell activation. In patients, higher serum predictive development. Overall, these results suggest CMKLR1/chemerin may be protective pathway for control