Autoimmune disease

Autoimmune disease has proven to be a unique conceptual and medical challenge, but hope for effective targeted therapies is tantalizingly close.

The thymus has a critical role in the establishment of appropriately educated and self-tolerant T cells. In their Focus Review, Cheng and Anderson discuss the most recent insights into how the thymus establishes self-tolerance.

T_reg cells have a critical role in maintaining peripheral tolerance. In this Focus Review, Dominguez-Villar and Hafler describe how the instability and plasticity of T_reg cells can contribute to the breakdown of tolerance and lead to autoimmune disease.

Autoimmune disease has been the subject of intense genetic study. In this Focus Review, Todd and colleagues describe recent advances and approaches in the genetic analysis of autoimmune disease.

The rates of autoimmune disease are rising more rapidly than can be explained by changes in genetics. In this Focus Review, Verdu and Danska describe the dietary and microbial influences on type 1 diabetes and draw comparisons with celiac disease.

In this Focus Review, Bar-Or and colleagues discuss the latest evidence that B cells play an important antibody-independent role in multiple sclerosis and the prospects this holds for therapeutic intervention.

A conversation with Shawn Rose, Director of Immunology Global Clinical Development, Janssen Research & Development, LLC

CD4⁺ T cell tolerance can be enforced by various mechanisms. Jenkins and colleagues use mice with entirely intact polyclonal T cell repertoires to comprehensively define the mechanisms of self-tolerance.

The development of experimental autoimmune encephalomyelitis has been attributed to cells of the T_H1 or T_H17 subset of helper T cells. Becher and Rostami and their colleagues show that IL-23-induced production of the cytokine GM-CSF underlies disease development and severity.

Autoimmunity can arise when tolerance mechanisms break down. Theofilopoulos and colleagues review how loss of peripheral tolerance, often driven by innate nucleic-acid sensors, leads to the activation of autoreactive lymphocytes that underlie many autoimmune diseases.