Potential Target for Severe Asthma, Other Chronic Inflammatory Diseases Identified

Potential Target for Severe Asthma, Other Chronic Inflammatory Diseases Identified

In a new study, researchers identified the role of platelets in the immune response, and discovered that the platelet-derived protein Dickkopf-1 (Dkk-1) contributes to chronic inflammation, having a pathological role in a series of conditions. Dkk-1 may represent a potential new therapeutic target for the treatment of severe asthma and other inflammatory diseases.

The research article, “The Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation,” was published in the journal Immunity.

From previous research it was known that Dkk-1, a protein produced by platelets (blood cells responsible for clotting), inhibits tissue repair, a feature that is common in chronic inflammatory disorders such as asthma, autoimmune diseases and cancer, where there is a constant activation of platelets with unhealed tissue damage.

In order to investigate the possible pathological role of Dkk-1 protein in inflammation, the research team, led by researchers at Yale University School of Medicine, studied the effect of a parasite and a common house-dust mite, a common cause for asthma, in normal mice and mice lacking the Dkk-1 protein.

Results showed that blocking Dkk-1 expression, either by genetic or pharmacological manipulation, protected the mice against asthma and parasitic infection. The researchers also observed that the protein induced the polarization of immune T cells towards an inflammatory phenotype, and that Dkk-1 provided a link between platelets, its major source during pathological inflammation, and lymphocytes (important white blood cells). Without Dkk-1, the innate and adaptive immune responses linked to chronic inflammation could not be triggered.

The study results also highlighted the importance of platelets in the immune system and tissue repair in response to inflammation. “Remarkably, without the presence of Dkk-1, both innate and adaptive immune responses for chronic inflammation could not be triggered,” first author Wook-Jin Chae said in a press release. “Because Dkk-1 is from platelets and it inhibits tissue repair, now we know how platelets become an essential part of the immune response and tissue repair simultaneously in response to inflammation.”

According to the study’s senior author, Alfred Bothwell, the discovery might even have a broader application.

“The potential in other chronic diseases such as cancer and autoimmunity is enormous. We are looking for small molecule compounds that could block Dkk-1-mediated signaling in the inflamed tissue,” the authors wrote.

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