Source of crucial immune cell in the skin discovered

Identification of precursor cell may lead to tumor immunotherapy as well as new treatment for rare disorder

Mount Sinai School of Medicine researchers have identified the precursors of cells in the skin that are part of the first line of defense against invading pathogens. The study will appear on Nature Immunology’s website this week and will be published in a future issue.

A tight network of cells covering the entire body is formed in the skin by a group of cells known as Langerhans cells. These cells ingest antigens present in the skin and transport them to lymph nodes, activating the immune system to protect the body against pathogens.

“Langerhans cells are particularly important to the development of tumor immunotherapy,” said Miriam Merad, MD, PhD, Assistant Professor of Gene and Cell Medicine at Mount Sinai and lead author of the study. “Most vaccines being developed for tumors are injected into the skin and rely on these cells to transport the antigen to the lymph nodes to trigger an immune response against the tumor.”

Once Langerhans cells transport an antigen, they need to be replaced to maintain the tight network in the skin. Dr. Merad and colleagues at Mount Sinai School of Medicine recently discovered that when skin is inflamed Langerhans cells are replaced by circulating precursor cells. They have now identified what this precursor cell is and identified a protein that is essential to the transformation of these precursor cells into Langerhans cells.

The researchers put fluorescent beads in mice in a group of immune cells known as monocytes. They then followed the cells to observe their fate. They found that a specific type of monocyte know as Gr-1 homes to inflamed skin, proliferates, and then differentiates to form Langerhans cells. They also found that a protein, called colony stimulating factor receptor (Csf-1) is necessary for the transformation of Gr-1 cells into Langerhans cells.

The researchers state that discovery of how Langerhans cells are replaced “should contribute to ongoing efforts to engineer immune responses in vaccine design and tumor immunotherapy and to a better understanding of the immune response against skin pathogens.”

“Now that we know which cells are the precursors to Langerhans cells and the importance of Csf-1, we may be able to enhance tumor vaccines by increasing the recruitment of Langerhans cell precursors to the skin,” said Dr. Merad.

Additionally, the researchers point out that the new findings hold promise for potential therapeutic for patients with a Langerhans histocytosis, a rare disease effecting approximately 200,000 children annually. In children with this disorder, large numbers of Langerhans cells infiltrate organs and tissues throughout the body. So, targeting the pathway by which these cells are formed could lead to new therapies to help children who now face the possibility of lifelong complications.

“It is known that Csf-1 levels are elevated in patients with Langerhans histocytosis,” said Dr. Merad. “Our findings indicated that finding ways to lower Csf-1 levels may produce new therapeutics for these patients.”