Humanizing the Mouse Immune System to Study Splanchnic Organ Inflammation

It is well known that alterations in splanchnic organ perfusion and/or immune regulation may produce inflammatory tissue injury similar to that observed in several human disorders such as ischaemia and reperfusion injury, food allergies, diabetes, inflammatory bowel disease and graft-versus-host disease. Mouse models have been tremendously important in defining the roles of the circulation, leukocyte trafficking, inflammatory mediator generation, immune regulation and the intestinal microbiota in the pathogenesis of acute and chronic inflammation. However, few of the promising interventions or therapeutics reported in mouse models of inflammatory diseases have been translated to clinically effective treatments in patients. There is growing concern that because of the significant differences that exist between the murine and human immune systems, mouse models may not adequately recapitulate the immuno-pathogenesis of inflammatory diseases. This inconvenient reality has prompted a number of investigators to undertake a series of studies to humanize the murine immune system via adoptive transfer of human lymphoid or progenitor cells into a new generation of immuno-deficient recipients. In this review, we summarize the recent advances that have been made in the development of humanized mice and describe how these mouse models are being used to study the pathophysiology of splanchnic organ inflammation. In addition, we discuss the limitations of the different approaches and present potential solutions for the continued improvement of these important animal models.