Experimental Models of Mucosal Inflammation
Warren Strober and Ivan J. Fuss
While studies of models of mucosal inflammation has been a mainstay of IBD research for the past half century, it is only in the last 10-15 years that this kind of study has taken its place as primus inter pares among the many approaches to studying these diseases. The reason this has come about is both simple and complex. It is simple because this period has seen the advent of a myriad of new models that individually and collectively allow the exhaustive exploration of many aspects of IBD that were formerly impossible in any other way. This includes the study of the possible effects of various types of genetic and immunologic abnormalities on disease pathogenesis and disease therapy. It is complex because the full and adequate exploration of these models inevitably requires an ability to apply a sophisticated knowledge of current molecular and cellular methodology to the study of living organisms. As attested to by the material reviewed here, the explosion in our knowledge of IBD derived from models is spectacular. With their use it has been possible to construct the main features of IBD on a detailed immunologic level, to explore the role of the bacterial microflora on disease pathogenesis, and to begin to understand the genetic underpinnings of the human disease. In addition, it has been possible to predict the efficacy of new treatments of the disease.
In this chapter we will review the main features of models of mucosal inflammation in three ways. First, we discuss the features of models that characterize the models as a whole and that therefore give rise to over-arching principles of mucosal inflammation that provide a sound basis of the human counterpart diseases. Second, we will consider two types of models (the cell-transfer model and the hapten-induced models) in considerable detail. These models are among those subjected to persistent in-depth study and have thus yielded a substantial fraction of the sum total of knowledge that has been gleaned from the study of all of the models. In addition, these models are among those most extensively studied and together they yield the majority of the insights that can be gleaned from the study of all models. Third and last, we have compiled a comprehensive table of all models of mucosal inflammation so that the models can be appropriately grouped and special insights that can be derived from each model can be briefly stated. While this tripartite approach should be very adequate in giving the reader a strong inkling of the models field, the reader is also encouraged to consult other recent reviews of this area including: Annual Review of Immunology191 and Nature Immunology Review.16