Pair of Studies Explore Role of Key Proteins in Psoriasis

November 29, 2019

Two recent studies have explored the role of activator protein-1 (AP-1), a transcription factor with a role in skin diseases caused by inflammation, including psoriasis and atopic dermatitis

Two recent studies have explored the role of activator protein-1 (AP-1), a transcription factor with a role in skin diseases caused by inflammation, including psoriasis and atopic dermatitis.

The first study, which appears in EMBO Molecular Medicine,1 used mouse models to identify genetic changes in hair follicles of skin cells, which can disrupt expression of AP-1 and trigger the inflammation that leads to psoriasis. The finding was important in showing how psoriasis starts with an external cause, such as stress, and not from an inherited disorder that alters genes.

“In the mouse model, we were able to show that the signal for the disease can be directed from the outside to the inside, and not just vice versa,” senior author and study team leader Erwin Wagner, PhD, of the Medical University of Vienna, said in a statement.

“If you switch off the target genes of the transcription factors, the inflammation is slowed down significantly,” Wagner said, pointing to potential therapeutic targets in psoriasis.

One potential target, thymic stromal lymphopoietin (TSLP) was singled out by researchers; Wagner said that when TSLP is inhibited, “the disease is almost stopped.”

A second study from this group previously highlighted the role of AP-1 proteins. In Cell Reports,2 the team showed that the proteins regulate the growth of bacteria, Staphylococcus aureus, in the skin afflict patients with atopic dermatitis, another inflammatory disease. The authors wrote that they also made additional observations about the role of T cells in controlling S. aureus, including how IL-17A affects bacteria growth.

The authors note that the cytokine IL-17 “is central to the pathogenesis of psoriasis,” and that IL-17 inhibition has “shown unprecedented success in the treatment of the disease.”

References

  1. Gago-Lopez N, Mellor LF, Megias D, et al. Role of bulge epidermal stem cells and TSLP signaling in psoriasis [published online September 26, 2019]. EMBO Mol Med. 2019; DOI: 10.15252/emmm.201910697.
  2. Uluckan O, Jimenez M, Roediger B, et al. Cutaneous immune cell-microbiota interactions are controlled by epidermal JunB/AP-1 [published online October 22, 2019]. Cell Reports. 2019; DOI: 10.1016/j.celrep.2019.09.042.