Possible involvement of CXCR3-CXCR6 + CD4 + T cells in Langerhans cell histiocytosis

Introduction Langerhans cell histiocytosis (LCH) is a condition characterized by proliferation of Langerhans cells and wide-range pathologies, ranging from single granulomatous lesions to multi-organ involvement, associated with tissue destruction. LCH pathogenesis remains obscure although association with interleukin (IL)-17A has been reported. We report here a case that illustrates the potential pathogenic role of helper T17 (Th17) cells in LCH-related bone destruction. Materials and Methods The patient was a 66-year-old woman. The clinical course included craniectomy and bone mass excision in X-9, diagnosis of LCH confirmed by histopathology, followed by 26-month chemotherapy. In August X, the patient was diagnosed with complete central diabetes insipidus. Symptoms improved after treatment with desmopressin. Pituitary magnetic resonance imaging showed swelling extending from the suprasellar region to the pituitary stalk, suggestive of LCH recurrence. This was followed by chemotherapy combined with mercaptopurine hydrate. Results Subsequent peripheral blood lymphocyte analysis showed marked increase in activated Th17 cells (CXCR3 − CXCR6 + CD4 + T cells). Double staining for CD4 and IL-17 by immunofluorescence of pathological tissue samples obtained during temporal bone mass excision, which confirmed the diagnosis of LCH in X-9, showed areas of combined presence of CD4-positive cells and IL-17-positive cells. Chemotherapy resulted in size reduction of the pituitary lesion and decrease in peripheral blood-activated Th17 cells. Conclusions We found abundant peripheral blood-activated Th17 cells and high percentages of IL-17-producing cells in osteolytic bone lesions in LCH. This finding, together with the decrease in peripheral blood-activated Th17 cells following chemotherapy, suggests the potential involvement of activated Th17 cells in LCH-related osteolysis.