Obese mice exhibit accelerated immune and myeloid reconstitution after congenic hematopoietic stem cell transplantation

Abstract

Abstract The obesity rate is increasing in the United States with more than a third of U.S. adults being obese. Obesity is a form of sterile chronic inflammation, termed “meta-inflammation”, which is local, chronic and triggered by metabolical pathways. Therefore, there is a need to uncover the potential role of obesity in the development of immune cell subsets post-HSCT. In this study, we wanted to assess the impact of obesity on immune reconstitution following congenic HSCT in lean and DIO (diet-induced obese) recipients. C57BL/6 mice received lethal radiation dose at 1100cGy and 5 million T cell-depleted bone marrow cells from H2-matched B6.SJL mice. Our data demonstrated that DIO recipients displayed a more rapid and robust reconstitution affecting both myeloid and lymphoid compartments. DIO recipients had increased neutrophils, platelets and total lymphocytes post-HSCT compared to control mice. Colony forming unit-granulocyte macrophage (CFU-GM) assays showed significantly higher numbers in DIO recipients at day 14 post-HSCT. Organ cellularity from thymus, spleen and bone marrow were increased in DIO recipients compared to lean mice at day 14 and 21 post-HSCT. Higher numbers of CD4+CD8+ thymocytes, as well as higher number of NK cells and B cells in the spleen and lymph nodes were also observed. Splenocytes from DIO recipients had greater proliferative ability either after stimulation with concanavalin A or in mixed lymphocyte reaction compared to lean controls. Taken together; these results indicated that obesity results in acceleration of engraftment and donor immune reconstitution.