Detection of IL-17A-producing peripheral blood monocytes in Langerhans cell histiocytosis patients

- Langerhans cell histiocytosis (LCH) monocytes produce IL-17A and RORγt.
- Both CD14high and CD14low blood monocytes produce IL-17A.
- Activation of healthy monocytes can result in IL-17A and RORC upregulation.
- High percentage of IL-17A+ monocytes in blood of LCH patients with active disease.
- Subgroup of LCH patients may benefit from IL-17A-targeted therapeutic interventions.

Langerhans cell histiocytosis (LCH) is a rare disease of unknown cause with manifestations ranging from isolated granulomatous lesions to life-threatening multi-system organ involvement. This disorder is further characterized by infiltration of immune cells in affected tissues and an association with interleukin (IL)-17A has been reported. Here, we investigated the presence of IL-17A-producing cells among peripheral blood mononuclear cells isolated from LCH patients and observed a high percentage of IL-17A+ monocytes in peripheral blood of LCH patients compared to controls. The IL-17A+ monocytes were also positive for the transcription factor retinoic acid orphan receptor (ROR) γt and showed increased mRNA levels for both IL-17A and RORγt. Notably, IL-17A was produced by all monocyte subsets and the expression level was positively associated with LCH disease activity. These data support a role for monocytes in the pathogenesis of LCH. Future therapeutic approaches may consider identification of patients who may benefit from IL-17A-targeted interventions.