The Transcription Factor Ets1 Suppresses T Follicular Helper Type 2 Cell Differentiation to Halt the Onset of Systemic Lupus Erythematosus.

A new therapeutic lead for lupus

31 July 2019

A new study explains why a single faulty gene can lead to lupus — a potentially fatal chronic disease in which the body’s immune system attacks its own organs and tissues.

A team led by researchers at the Institute for Basic Science engineered various strains of mice, each with a different immune cell population that lacked a working copy of Ets1, a gene linked to lupus in people. Only those mice with Ets1-deficient helper T cells developed a lupus-like autoimmune condition. Those animals showed a proliferation of an immune cell known as a T follicular helper type 2 (Tfh2) cell.

The researchers found that Ets1 normally blocks Tfh2 expansion and an immune signalling molecule called interleukin-4 activates the process. They also demonstrated that blocking interleukin-4 helped reduce Tfh2 levels and ameliorate lupus progression in the mouse model.

The team found that the frequency of Tfh2 cells tracks with disease severity in lupus-affected individuals, suggesting that targeting IL-4 could offer therapeutic benefit to patients.

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References

1. Immunity 49, 1034–1048.e8 (2018). doi: 10.1016/j.immuni.2018.10.012