Novel therapeutic target found for psoriasis

John Murphy, MDLinx | June 13, 2016

Scientists have determined that a protein, expressed by B lymphocytes, contributes to psoriasis by suppressing anti-inflammatory cytokines. When the researchers eliminated this protein in an experimental mouse model of psoriasis, skin inflammation in the mice didn’t occur, according to a recent study published in the journal Nature Communications.


Anti-inflammatory therapeutic target found for psoriasis

In psoriasis (A), scientists found that B lymphocytes play a role in skin inflammation (+), as compared to healthy skin (B). This finding provides a drug target to suppress this inflammation. (Photos: Würzburg University Hospital Dermatology Clinic)

Many different cells are known to be involved in psoriasis. For this study, scientists focused on B lymphocytes, a cell type that hasn’t been well investigated in this disease.

To understand the role of B cells in skin inflammation, the researchers bred mice that had nearly no B cells. Then the researchers induced a psoriasis-type condition in these mice, and the mice showed high levels of inflammation, which illustrated the importance of B cells in counteracting the inflammation of psoriasis.

Next, when the researchers transferred B cells into these mice, they observed that the mice had a significant decrease in skin inflammation. Interestingly, when the researchers bred mice with B cells but without a specific transcription factor protein expressed by those B cells, these mice had comparatively less inflammation, too.

This meant that the B lymphocytes produced the anti-inflammatory cytokines, but the transcription factor protein suppressed the cytokines’ anti-inflammatory effect.

“It was crucial to find out that synthesis of the anti-inflammatory cytokine IL-10 by the B lymphocytes through the interaction with the protein ‘nuclear factor of activated T cells’ (NFATc1), a transcription factor, was reduced,” said Matthias Goebeler, MD, Professor in the Department of Dermatology, Venerology, and Allergology at Würzburg University Hospital, in Würzburg, Germany.

This finding suggests that a therapy that could restore IL-10 anti-inflammatory levels would be a benefit for psoriasis patients.

“By uncovering more details about the interaction, we could develop drugs that suppress the inflammatory processes in psoriasis even more specifically in the future,” Dr. Goebeler added.

NFATc1 might be the target to do so. The researchers noted that NFATc1’s enhanced expression in other psoriatic skin cells—not just in B cells—likely also contributes to the disease. In T cells, for example, NFATc1 stimulates the expression of several genes that are highly expressed during psoriasis.