Scleroderma is an autoimmune disease affecting the connective tissues of the body. This rare disease affects women more than men and is characterized by tightening and hardening of the skin; however, the joints and many other parts of the body are also affected leading to pain and various types of organ dysfunction. Treatment for scleroderma is primarily symptomatic because there is no cure, but this may change for the better thanks to an immunological discovery that may open the door to more direct treatment of the underlying problem.
A group of researchers from the Hospital for Special Surgery, New York, NY found that specific immune cells, plasmacytoid dendritic cells, play key roles in the scleroderma disease process. These dendritic cells promote inflammation seen with autoimmune diseases, including those involving the skin, via the toll-like receptor. However, the role of these cells in the fibrotic process seen with scleroderma is not completely clear. Therefore, the researchers conducted a study to determine how plasmacytoid cells may mediate this process in scleroderma.
By studying plasmacytoid dendritic cells from patients and depleting these cells in a mouse model of scleroderma, they observed that these dendritic cells remain activated in the skin of patients with scleroderma and cause secretion of key cytokines associated with the disease, interferon-alpha and CXCL4. Even more striking and revealing was the prevention or reversal of fibrosis seen in mice when the plasmacytoid dendritic cells were depleted. This showed that these cells not only contribute to the inflammatory immune response, but to the fibrotic process that is characteristic of scleroderma.
Armed with this new information, new treatment strategies targeting plasmacytoid dendritic cells can provide therapy that is not just symptomatic, but can attack the underlying cellular processes that cause the debilitating signs and symptoms. Using existing antibody drugs that target these cells can be explored and represent an effective approach to scleroderma treatment. New drugs can also be designed that inhibit target toll-like receptor, interferon-alpha, or CXCL4 signaling to provide significant relief for people with scleroderma.