| http://purl.uniprot.org/citations/36542690 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/36542690 | http://www.w3.org/2000/01/rdf-schema#comment | "Acute graft-versus-host disease (aGVHD), which is driven by allogeneic T cells, has a high mortality rate and limited treatment options. Human β-defensin 2 (hBD-2) is an endogenous epithelial cell-derived host-defense peptide. In addition to its antimicrobial effects, hBD-2 has immunomodulatory functions thought to be mediated by CCR2 and CCR6 in myeloid cells. In this study, we analyzed the effect of recombinant hBD-2 on aGVHD development. We found that intestinal β-defensin expression was inadequately induced in response to inflammation in two independent cohorts of patients with aGVHD and in a murine aGVHD model. Treatment of mice with hBD-2 reduced GVHD severity and mortality and modulated the intestinal microbiota composition, resulting in reduced neutrophil infiltration in the ileum. Furthermore, hBD-2 treatment decreased proliferation and proinflammatory cytokine production by allogeneic T cells in vivo while preserving the beneficial graft-versus-leukemia effect. Using transcriptome and kinome profiling, we found that hBD-2 directly dampened primary murine and human allogeneic T cell proliferation, activation, and metabolism in a CCR2- and CCR6-independent manner by reducing proximal T cell receptor signaling. Furthermore, hBD-2 treatment diminished alloreactive T cell infiltration and the expression of genes involved in T cell receptor signaling in the ilea of mice with aGVHD. Together, we found that both human and murine aGVHD were characterized by a lack of intestinal β-defensin induction and that recombinant hBD-2 represents a potential therapeutic strategy to counterbalance endogenous hBD-2 deficiency."xsd:string |
| http://purl.uniprot.org/citations/36542690 | http://purl.org/dc/terms/identifier | "doi:10.1126/scitranslmed.abp9675"xsd:string |
| http://purl.uniprot.org/citations/36542690 | http://purl.uniprot.org/core/author | "Duyster J."xsd:string |
| http://purl.uniprot.org/citations/36542690 | http://purl.uniprot.org/core/author | "Schiff M."xsd:string |
| http://purl.uniprot.org/citations/36542690 | http://purl.uniprot.org/core/author | "Schell C."xsd:string |
| http://purl.uniprot.org/citations/36542690 | http://purl.uniprot.org/core/author | "Boerries M."xsd:string |
| http://purl.uniprot.org/citations/36542690 | http://purl.uniprot.org/core/author | "Bhatt A.S."xsd:string |
| http://purl.uniprot.org/citations/36542690 | http://purl.uniprot.org/core/author | "Haring E."xsd:string |
| http://purl.uniprot.org/citations/36542690 | http://purl.uniprot.org/core/author | "Schmitt-Graeff A."xsd:string |
| http://purl.uniprot.org/citations/36542690 | http://purl.uniprot.org/core/author | "Jensen B.A.H."xsd:string |
| http://purl.uniprot.org/citations/36542690 | http://purl.uniprot.org/core/author | "Wehkamp J."xsd:string |
| http://purl.uniprot.org/citations/36542690 | http://purl.uniprot.org/core/author | "Kohler N."xsd:string |
| http://purl.uniprot.org/citations/36542690 | http://purl.uniprot.org/core/author | "Aumann K."xsd:string |
| http://purl.uniprot.org/citations/36542690 | http://purl.uniprot.org/core/author | "Minguet S."xsd:string |
| http://purl.uniprot.org/citations/36542690 | http://purl.uniprot.org/core/author | "Zeiser R."xsd:string |
| http://purl.uniprot.org/citations/36542690 | http://purl.uniprot.org/core/author | "Andrieux G."xsd:string |
| http://purl.uniprot.org/citations/36542690 | http://purl.uniprot.org/core/author | "Kissel S."xsd:string |
| http://purl.uniprot.org/citations/36542690 | http://purl.uniprot.org/core/author | "Doetsch S."xsd:string |
| http://purl.uniprot.org/citations/36542690 | http://purl.uniprot.org/core/author | "Kolter J."xsd:string |
| http://purl.uniprot.org/citations/36542690 | http://purl.uniprot.org/core/author | "Ruckert T."xsd:string |
| http://purl.uniprot.org/citations/36542690 | http://purl.uniprot.org/core/author | "Woessner N.M."xsd:string |
| http://purl.uniprot.org/citations/36542690 | http://purl.uniprot.org/core/author | "Siranosian B.A."xsd:string |
| http://purl.uniprot.org/citations/36542690 | http://purl.uniprot.org/core/author | "Braun L.M."xsd:string |
| http://purl.uniprot.org/citations/36542690 | http://purl.uniprot.org/core/author | "Nordkild P."xsd:string |