Chapter 27 - Animal Models of Organ-Specific Autoimmune Disease

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Abstract

Organ-specific autoimmune diseases are a loosely defined collection of disorders characterized by broadly shared aspects of presumed pathogenesis (i.e., the interplay of genetic predispositions, environmental insults, and destructive immune responses) and a relative restriction of pathology to defined cell types, tissues, and/or organs. Our understanding of these complex conditions has been decisively advanced through the study of suitable animal models and herein we outline their general utility and promise as well as their limitations and pitfalls; we also provide a survey of individual research strategies that seek to model the 17 most prevalent organ-specific autoimmune disorders and that collectively account for ~75% of all human autoimmune disease cases. Building largely on the established concepts and hypotheses but facilitated and accelerated by remarkable technological advances, many new, refined, and improved animal models have been introduced in the early 21st century. Altogether, they have considerably enriched our knowledge about fundamental immunological processes in health and autoimmune disease yet the degree to which they have precipitated therapeutic progress is less clear. The reasons for this shortcoming are undoubtedly manifold, but we contend that it is above all a relative “lack of diversity” that has compromised the reproducibility, robustness, and relevance of preclinical animal studies. A truly effective integration of animal models into organ-specific autoimmune disease research will not only have to tackle these issues but also needs to be principally informed by a more detailed pathophysiological description of the respective human diseases.

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