How a Single Faculty Gene Can Lead to Lupus
How a Single Faculty Gene Can Lead to Lupus
  • Reporter Ryu Nu-ri
  • 승인 2019.01.05 00:36
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A research team at the Academy of Immunology and Microbiology, within the Institute for Basic Science (IBS) & POSTECH in has discovered the role of a key gene involved in the autoimmune disease, systemic lupus erythematosus (SLE) or lupus for short. In the December issue of Immunity, the scientists reported that defects in Ets1 gene in both mice and humans are linked to some of the characteristic SLE immunity abnormalities, and found a potential therapeutic candidate.

SLE is a chronic disease where the immune system uses autoantibodies to erroneously attack multiple healthy organs and tissues. There are no complete cures but there are only treatments to alleviate symptoms. Genetic factors strongly influence SLE development. Over 60 genes have been linked to this disease so far, but have not been fully analyzed yet. In this study, IBS/POSTECH researchers concentrated on the Ets1 gene, one of the top four genes associated with SLE in Asian population.

They discovered that getting rid of Ets1 in CD4+ T cells specifically was sufficient for the development of SLE-like autoimmunity. Upon further evaluation, the team discovered that Ets1 is involved in controlling the expansion of a newly-described class of immune cells, known as T follicular helper type 2 (Tfh2) cells.

Tfh2 cells interact with antibody-producing cells (B cells) in lymph nodes and the spleen, causing them to produce autoantibodies. The researchers found that Ets1 works as a restriction gate that halts the expression of key Tfh2 genes, thereby blocking Tfh2 expansion. Thus, when Ets1 is missing or mutated, like in SLE, Tfh2 cells are free to expand, leading to unnecessary autoantibody production. The researchers observed this phenomenon in both mouse and human SLE cases.

Remarkably, the research team could also mitigate some SLE features by blocking a key component in the autoantibody production pathway known as IL4. After treating mice with anti-IL4, the scientists observed a reduction in spleen size and number of autoantibody-producing cells. This strongly suggests the use of IL4 blocking therapy for patients with low Ets1 expressions and expanded Tfh2 populations.

 


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