Kidney Immune Cell Characterization of Humanized Mouse Models

Abstract

Key Points Experimental studies often fail to translate to clinical practice. Humanized mouse models are an important tool to close this gap.We immunophenotyped the kidneys of NOG (EXL) and NSG mouse strains engrafted with human CD34+ hematopoietic stem cells or PBMCs and compared with immune cell composition of normal human kidney.Human CD34+ hematopoietic stem cell engraftment results in steady renal immune cell populations in mouse kidney with key similarities in composition compared with human kidney. Successful translation of experimental mouse data to human diseases is limited because of biological differences and imperfect disease models. Humanized mouse models are being used to bring murine models closer to humans. However, data for application in renal immune cell–mediated diseases are rare. We therefore studied immune cell composition of three different humanized mouse kidneys and compared them with human kidney. NOG and NOGEXL mice engrafted with human CD34+ hematopoietic stem cells were compared with NSG mice engrafted with human PBMCs. Engraftment was confirmed with flow cytometry, and immune cell composition in kidney, blood, spleen, and bone marrow was analyzed in different models. The results from immunophenotyping of kidneys from different humanized mouse strains were compared with normal portions of human kidneys. We found significant engraftment of human immune cells in blood and kidney of all tested models. huNSG mice showed highest frequencies of hTCR+ cells compared with huNOG and huNOGEXL in blood. huNOGEXL was found to have the highest hCD4+ frequency among all tested models. Non-T cells such as hCD20+ and hCD11c+ cells were decreased in huNSG mice compared with huNOG and huNOGEXL. Compared with normal human kidney, huNOG and huNOGEXL mice showed representative immune cell composition, rather than huNSG mice. In summary, humanization results in immune cell infiltration in the kidney with variable immune cell composition of tested humanized mouse models and partially reflects normal human kidneys, suggesting potential use for translational studies.