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Autoimmune Diseases
Volume 2014, Article ID 452853, 12 pages
http://dx.doi.org/10.1155/2014/452853
Review Article

The Role of Decay Accelerating Factor in Environmentally Induced and Idiopathic Systemic Autoimmune Disease

1Department of Ophthalmology, Duke University School of Medicine, Albert Eye Research Institute, Durham, NC 27710, USA
2Department of Surgery and Center for Investigations of Health and Education Disparities, University of California, San Diego, La Jolla, CA 92037, USA
3Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA

Received 10 October 2013; Accepted 19 November 2013; Published 27 January 2014

Academic Editor: Aristo Vojdani

Copyright © 2014 Christopher B. Toomey et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Decay accelerating factor (DAF) plays a complex role in the immune system through complement-dependent and -independent regulation of innate and adaptive immunity. Over the past five years there has been accumulating evidence for a significant role of DAF in negatively regulating adaptive T-cell responses and autoimmunity in both humans and experimental models. This review discusses the relationship between DAF and the complement system and highlights major advances in our understanding of the biology of DAF in human disease, particularly systemic lupus erythematosus. The role of DAF in regulation of idiopathic and environmentally induced systemic autoimmunity is discussed including studies showing that reduction or absence of DAF is associated with autoimmunity. In contrast, DAF-mediated T cell activation leads to cytokine expression consistent with T regulatory cells. This is supported by studies showing that interaction between DAF and its molecular partner, CD97, modifies expression of autoimmunity promoting cytokines. These observations are used to develop a hypothetical model to explain how DAF expression may impact T cell differentiation via interaction with CD97 leading to T regulatory cells, increased production of IL-10, and immune tolerance.