Researchers identify origins of Langerhans cell histiocytosis in children

Researchers identify origins of Langerhans cell histiocytosis in children
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The origins of Langerhans cell histiocytosis have been identified by researchers from Karolinska Institutet in collaboration with Karolinska University Hospital.

Langerhans cell histiocytosis is a serious type of cancer-like disease that mainly affects children and can be fatal in severe cases. Around five to ten children are diagnosed with the condition in Sweden every year, usually before the age of ten. It causes a cancer-like mutation in the immune cells, which otherwise detect and eliminate cancer cells.

“The origin of the Langerhans cell histiocytosis cells has been discussed for decades. Some researchers are convinced that Langerhans cell histiocytosis is derived from a certain type of immune cell called dendritic cells, while others believe that they come from related cells called monocytes,” said Egle Kvedaraite, a doctor and researcher at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet and first author of the new study.

The findings were published in Science Immunology.

Understanding the history of Langerhans cell histiocytosis

The researchers from Karolinska Institutet and a team of scientists from Singapore Immunology Network and Newcastle University have been able to show that both theories are close to the truth. The researchers combined single-cell sequencing, the microscopy of samples and the tracking of cells from patients recruited from, among others, Karolinska University Hospital.

The researchers discovered that mutated Langerhans cell histiocytosis cells had properties similar to both monocytes and dendritic cells, and the newly discovered type of dendritic cells is called dendritic cell type 3 (DC3).

“Today we know that DC3 has a separate pathway of development, separate from other dendritic cells and monocytes, and knowledge of this was crucial in our study,” said Egle Kvedaraite.

Different cells can communicate and promote the development of the disease

The researchers also found that the different cell types could communicate with each other to promote the development of Langerhans cell histiocytosis, creating a self-reinforcing effect.

“Among the treatment options for Langerhans cell histiocytosis, targeted therapy can be successfully applied, but the disease comes back when the targeted treatment is discontinued. This poses a serious challenge for patients, as a lifelong treatment for children is not a good option given the side effects,” added Egle Kvedaraite.

The new understanding of the origin of this condition may lead to the development of new targeted treatments.

“The findings could lead to a treatment aimed at eliminating the pathological cells,” said Egle Kvedaraite.

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