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Cold Spring Harb Perspect Biol. 2012 Nov 1;4(11). pii: a007542. doi: 10.1101/cshperspect.a007542.

Current and future immunomodulation strategies to restore tolerance in autoimmune diseases.

Author information

1
UCSF Diabetes Center, University of California at San Francisco, 94143, USA. Jeff.Bluestone@ucsf.edu

Abstract

Autoimmune diseases reflect a breakdown in self-tolerance that results from defects in thymic deletion of potentially autoreactive T cells (central tolerance) and in T-cell intrinsic and extrinsic mechanisms that normally control potentially autoreactive T cells in the periphery (peripheral tolerance). The mechanisms leading to autoimmune diseases are multifactorial and depend on a complex combination of genetic, epigenetic, molecular, and cellular elements that result in pathogenic inflammatory responses in peripheral tissues driven by self-antigen-specific T cells. In this article, we describe the different checkpoints of tolerance that are defective in autoimmune diseases as well as specific events in the autoimmune response which represent therapeutic opportunities to restore long-term tolerance in autoimmune diseases. We present evidence for the role of different pathways in animal models and the therapeutic strategies targeting these pathways in clinical trials in autoimmune diseases.

PMID:
23125012
PMCID:
PMC3536337
DOI:
10.1101/cshperspect.a007542
[Indexed for MEDLINE]
Free PMC Article
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