Kidney Immune Cell Characterization of Humanized Mouse Models

Abstract

Successful translation of experimental mouse data to human diseases is limited due to 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 is 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 blood, spleen and bone marrow was analyzed in different models. 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 to huNOG and huNOGEXL in blood. huNOGEXL was found to have the highest hCD4+ frequency amongst all tested models. Non-T cells such as hCD20+ and hCD11c+ cells were decreased in huNSG mice compared to huNOG and huNOGEXL. Compared to “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 are able to partially reflect normal human kidneys suggesting potential use for translational studies.