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Modelling Gene-Environment Interactions in Th1- and Th2-Dominated Diseases of Laboratory Animals

  • G. A. W. Rook
  • R. Martinelli
  • L. Rosa Brunet
Conference paper
Part of the Ernst Schering Research Foundation Workshop book series (SCHERING FOUND, volume 50)

3.6 Conclusions

In conclusion, the “old friends hypothesis” seeks to explain the increasing prevalence of many chronic inflammatory disorders as a failure of immunoregulation secondary to decreased exposure to certain microorganisms that have been present throughout our evolutionary history. It is argued that these organisms are effectively part of our physiology, and are recognised as harmless by the innate immune system, which then activates immunoregulatory circuits, including Treg and regulatory APCs. The “old friends” consequently act as adjuvants for other antigens such as self, allergens, and gut contents, and so limit chronic inflammatory immunoregulatory disorders. These mechanisms can be revealed by altering the microbial exposure, or by studying the presence of polymorphisms of the innate immune system, since these two factors provide a series of classical gene-environment interactions. An important consequence of this understanding is the fact that the enormous variability of animal models of inflammatory disorders in different laboratories can now be exploited to investigate these gene-environment interactions. Experiments based on these differences, perhaps involving collaborations between laboratories, or the use of gnotobiotic mice reconstituted with one or a few microbial species, can be applied to those animal models where variable microbial exposure is already known to exert a profound influence.

Keywords

Innate Immune System Allergy Clin Immunol Hygiene Hypothesis Microbial Exposure Nate Immune System 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • G. A. W. Rook
    • 1
  • R. Martinelli
    • 2
  • L. Rosa Brunet
    • 2
  1. 1.Centre for Infectious Diseases and International Health, Windeyer Institute of Medical SciencesRoyal Free and University College Medical SchoolLondonUK
  2. 2.SR Pharma, Windeyer Institute of Medical SciencesRoyal Free and University College Medical SchoolLondonUK

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