Activation of the protein known as aryl hydrocarbon receptor (AhR), reduces inflammation in the skin of patients with psoriasis, according to a study published in Immunity.

Previous studies have shown that AhR, a transcription factor that senses environmental stimuli, modulates pathology in psoriasis and helps control the body’s response to toxins such as environmental pollutants, or toxins produced by the body.

After combining data from an analysis of psoriasis patient skin biopsies with data from a mouse model of psoriasiform inflammation, researchers from the National Institute for Medical Research in London combined data from an analysis of psoriasis patient skin biopsies with data from a mouse model of psoriasiform inflammation.


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Immune cells were not the primary cause for the hyperreactivity observed in Ahr-deficient mice, the investigators reported. Rather, the response of nonhematopoietic skin cells to inflammatory stimuli was severely dysregulated in the absence of AhR, according to the study data.

These findings are significant because the current focus for therapeutic intervention in psoriasis is on modulating inflammatory immune parameters, such as interleukin-17 (IL-17), IL-12, IL-23 or TNF, which are the immune drivers of skin pathology in both human disease and the mouse model.

“Our data emphasize the cross-talk between cells of the immune system and nonhematopoetic cells during inflammation, and it is now widely recognized that such interactions crucially underpin both the homeostasis of the skin environment and its dysregulation in diseases such as psoriasis,” the researchers concluded.

“Beneficial effects of AhR activation open the possibility of therapeutic intervention in chronic inflammatory skin disease, but further research is needed to understand the mechanism underlying the physiological consequences of AhR signaling in the immune system.”

References

  1. Di Meglio P. Immunity. 2014; 40: 989–1001.

Disclosure: This work was supported through the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London.