The immune system takes a divide-and-conquer approach to launching and maintaining psoriasis flares, according to a study analyzing psoriasis plaques. By tracking the activity of dendritic cells, a kind of immune cell, before and during flares, researchers discovered that one kind of dendritic cell helps trigger plaque formation, while another determines how bad that plaque gets.
The study appeared in the September 2014 issue of EMBO Molecular Medicine.
Dendritic cells are a type of immune cell known as antigen-presenting cells, which means that they tell other immune cells when to launch an inflammatory attack. They have several different subtypes, including the two that the researchers focused on: Langerhans cells (LCs), which are found in the skin, and plasmacytoid dendritic cells (pDCs), which circulate in the blood.
Analyzing skin from psoriasis patients, as well as mice genetically modified to develop the disease, researchers found that psoriatic skin had increased levels of pDCs and decreased levels of LCs. Using that as a starting point, researchers then adjusted the levels of pDCs and LCs in mice to see if that changed the severity of flares.
Reducing the level of pDCs before initiating a psoriasis flare made the flare significantly less severe, researchers report. But reducing pDCs when a flare was already underway had no effect on severity. From that, researchers determined that the job of pDCs is to trigger the formation of new plaques.
On the other hand, researchers found, reducing LCs before initiating a flare had no effect, but reducing LCs during a flare made symptoms more severe. That told researchers that the depletion of LCs in psoriasis plaques makes those plaques worse.
Targeting dendritic cells for treatment
Different dendritic cells have different effects on psoriatic flares because they secrete different kinds of cytokines, the researchers report. Cytokines are proteins involved in inflammatory responses. Many cytokines promote inflammation, but some are anti-inflammatory.
The researchers report that pDCs produce interferon-1, a pro-inflammatory cytokine, while LCs produce interleukin-10 (IL-10), an anti-inflammatory cytokine. When LCs are decreased, they explain, IL-23, a pro-inflammatory cytokine linked to psoriatic disease, is increased, which makes a plaque more inflamed.
Putting all this together, researchers concluded that pDCs are the culprits behind new psoriasis flares, while LCs can help reduce inflammation. But if LCs are decreased — which is the case in plaques — then that leaves room for pro-inflammatory cytokines to move in and make the plaque worse.
These findings could lead to new therapeutic strategies for fighting psoriasis that involve adjusting the levels of certain dendritic cells, the researchers note. According to Dr. Maria Sibilia, a researcher in Austria and the senior author of the study, these treatments would likely be topical, and would work to modulate the release of cytokines.
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