TACI: A new target for treating lupus

Removing the molecule TACI from immune cells in mice with lupus protects against the disease without compromising immunity.

Removing the molecule TACI from immune cells in mice with lupus protects against the disease without compromising immunity.

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Removing a molecule called TACI from immune cells protects mice with lupus from the disease without compromising their natural immunity.

The discovery was made by a research team led by Professor Fabienne Mackay from the School of Biomedical Sciences at the University of Melbourne.

The autoimmune disease lupus is associated with excessive amounts of a protein called B-cell activating factor (BAFF). BAFF normally activates B cells to produce antibodies for fighting infections and cancer, but too much BAFF leads to the production of autoantibodies. These autoantibodies attack tissues and organs such as the joints, skin, kidneys, blood cells, brain, heart and lungs. Current lupus treatments block BAFF, which helps to manage symptoms but leaves patients vulnerable to complications like infections.

BAFF binds to two different receptors on the surface of B cells. Professor Mackay’s team discovered that one of these receptors, called TACI (for 'transmembrane activator and CAML interactor’), is required to produce autoantibodies.

The researchers showed that removing TACI from B cells decreased the BAFF-induced production of autoantibodies in mice with lupus without affecting normal B cell function. This suggests that molecules blocking TACI in humans could be used as lupus therapies without leaving patients vulnerable to infection.

Next steps

Professor Mackay’s team, which is based at the Peter Doherty Institute for Infection and Immunity, is developing lupus treatments that work by blocking TACI.

Funding

NHMRC Development Grant to Professor Fabienne Mackay

Molecular control of B-cell homeostasis in health and malignancy (APP1113659)

Victorian State Government Operational Infrastructure Support

Publication

Figgett WA et al (2015) Deleting the BAFF receptor TACI protects against systemic lupus erythematosus without extensive reduction of B cell numbers. Journal of Autoimmunity 61: 9–16. doi: 10.1016/j.jaut.2015.04.007

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First published on 30 March 2022.


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