The Role of Macrophages in the Development of Human Renal Allograft Fibrosis in the First Year After Transplantation

Inflammatory macrophage–associated 3-gene signature predicts subclinical allograft injury and graft survival

“…We also demonstrated that the CRM is mechanistically involved in graft injury by identifying two FDA-approved drugs that reduced graft-infiltrating immune cells and extended graft survival in a mouse model of cardiac transplantation and electronic health records of renal transplant patients (7). Collectively, these results suggest the possibility of a gene signature common to both ACR and AMR (10)(11)(12).…”

“…Studies of acute and chronic rejecting human allografts with panels of macrophage polarization markers are necessary to extend the understanding of macrophage polarization in transplant rejection. Toki et al contributed to this objective by staining for two markers of M2 macrophages (CD163 and CD206) in 46 human renal allograft biopsies (10). While the majority of CD68-positive cells coexpressed CD206 in ACR (98.7%) and AMR (73.5%), transcriptional profiles of the 12-month biopsies revealed that inflammatory and IFN-γ signaling genes were associated with interstitial fibrosis/tubular atrophy.…”

“…Macrophage infiltration has been implicated in both AR (13) and chronic graft failure (10,11), yet a precise role for this cell type in organ transplantation remains unclear (12). Macrophages take on diverse phenotypic states in response to environmental stimuli, with activation characterized by a spectrum of transcriptional reprogramming (14), ranging from an antiinflammatory phenotype in the presence of IL-4 or IL-10 to a proinflammatory phenotype in the presence of IFN-γ, referred to as M(IL-4), M(IL-10), and M(IFN-γ), respectively (15).…”

IL-34 mediates acute kidney injury and worsens subsequent chronic kidney disease

“…For example, the abundance of M2-like Mø in human and mouse polycystic kidney disease (PKD), contribute to the progression of renal disease by promoting cyst growth and fibrosis (50). Similarly, M2-like Mø proliferation and infiltration is associated with tubular injury and progression of fibrosis during inflammation in human kidney transplant allografts (51,52). Moreover, insufficient renal epithelial healing in mice promotes an expansion of M2-like Mø that accelerates fibrogenesis (reviewed in ref.…”

CD4+ T lymphocytes produce adiponectin in response to transplants

“…We have reported previously that T cells are required to orchestrate the progressive macrophage infiltrates that are a prominent component of chronic arterial pathology in cardiac allograft rejection (15). Several studies have associated wound-healing macrophages with aspects of chronic rejection in cardiac and renal allografts (21)(22)(23). The mediators that modulate macrophages in transplants have not been elucidated.…”