The adaptor protein TASL is required for age-related B cell emergence and lupus-like disease development in mice

TL;DR

This study shows that the protein TASL is important for B cell activation and the development of lupus-like disease in mice, suggesting it could be a target for treatment.

Contribution

The study identifies TASL as a key player in B cell activation and lupus development in a mouse model.

Findings

TASL is required for full B cell activation via TLR9 stimulation and interferon signaling.

TASL is crucial for the emergence of age-associated B cells and IgG2c antibody production.

Deleting TASL prevents autoimmunity in the B6.MRLlpr lupus model.

Abstract

The autoimmune disease systemic lupus erythematosus (SLE) is associated with genetic variants in the X-linked gene CXORF21, which encodes the protein TASL. TASL acts as an adaptor in the IRF5 pathway and is necessary for the phosphorylation of IRF5 in response to TLR7 or TLR9 stimulation. Here, we investigate the role of TASL in the humoral immune response, and in the development of lupus in the B6.MRLlpr murine model of SLE. We find that while TASL is dispensable for their development, it is required for the full activation of B cells via TLR9 stimulation, and consequent interferon signaling and inflammatory cytokine expression. Additionally, TASL is crucial for the emergence of age-associated B cells (ABCs), a B cell population derived from the extrafollicular response that increases with age and is expanded in autoimmune disease, and the production of IgG2c antibodies. We also find that deletion of TASL prevents the onset of autoimmunity in the genetically-determined B6.MRLlpr model of lupus.

Systemic lupus erythematosus is a chronic autoimmune disease that mostly affects women and it is associated with genetic variants in the X-linked gene encoding the adaptor protein TASL. This study shows that TASL is required for B cell activation, age-associated B cell formation and lupus-like development in a mouse model, suggesting its potential as a therapeutic target.

Figures