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This Month in AJP

    Published:December 14, 2021DOI:https://doi.org/10.1016/j.ajpath.2021.12.001

        Modeling Obliterative Bronchiolitis

        Obliterative bronchiolitis (OB) following lung transplantation is an irreversible lethal complication. Using a tracheal transplant mouse model of OB, Krebs et al (Am J Pathol, 254–269) studied the effect of vascular endothelial growth factor receptors (VEGFRs) 1 and 2 in the development of obliterative airway disease (OAD). OAD was induced by heterotopically transplanting fully major histocompatibility complex–mismatched mouse tracheal allografts. Blocking VEGFR significantly decreased the innate and adaptive immune responses and the development of OAD, likely by inhibiting these receptors on epithelial and endothelial cells of the airways wall. Targeting VEGFR signaling may help manage OB following lung transplantation.

        Managing Graft Survival Post Corneal Transplantation

        The rate of corneal endothelial cell (CEnC) loss increases post corneal transplantation, which can threaten sight. Using human and mouse CEnC lines and a mouse model, Lužnik Marzidovšek et al (Am J Pathol, 270–280) studied the role of the cytoprotective neuropeptide alpha-melanocyte-stimulating hormone (α-MSH) on corneal transplantation. The α-MSH receptor melanocortin 1 receptor (MC1R) is highly expressed on CEnCs. In vitro and in MC1R signaling-deficient mice, α-MSH had cytoprotective effects on CEnCs post corneal transplantation. In vivo, the loss of MC1R signaling significantly reduced long-term graft survival. Targeting α-MSH/MC1R signaling may enhance graft survival post corneal transplantation.

        Understanding Podocyte Injury

        Podocyte injury can aggravate chronic kidney diseases (CKDs). Using single-cell RNA sequencing of glomerular-enriched kidney tissue from an inducible mouse model of a progressing glomerular disease, Clark et al (Am J Pathol, 281–294) studied the effects of podocyte injury at a single-cell resolution after a week of disease induction. Data reveal the initial changes within the kidney filter and point to novel actionable markers that may be therapeutically targeted to manage CKDs.

        Linking Gut Inflammation to Brain Immune Repopulation

        Peripheral monocyte-derived CX3CR1+ cells promote immune repopulation of the brain parenchyma and gut after systemic inflammation. Using adoptive bone marrow transfer from fluorescently labelled CX3CR1 reporter mice, Batra et al (Am J Pathol, 295–307) studied the underlying mechanisms. Colon inflammation and injury increased tissue colonization by labelled CX3CR1 cells, promoted brain colonization by peripheral labelled CX3CR1 cells, and increased recruitment and association of labelled CX3CR1 cells with the vessel wall, macrophage colonization of the colon and the brain, and macrophage chemotactic ligands in the brain. Gut inflammation affects the repopulation of the brain and intestines and may have dramatic clinical implications on neurologic outcomes in health and disease.

        Classifying Cancer

        miRNAs are excellent classification markers. Using miRNA expression profiles from over 1000 human breast and skin tissue samples, Kaczmarek et al (Am J Pathol, 344–352) adapted an existing deep learning–based deep cancer classifier (DCC) to discriminate neoplastic and non-neoplastic samples. This adapted DCC outperforms traditional machine learning and feature selection approaches, and may be useful in identifying miRNA biomarkers using a custom feature selection algorithm.

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