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

Akemi Tokutsu; Yosuke Okada; Akira Kurozumi; Kenichi Tanaka; Satoshi Kubo; Yoshiya Tanaka

doi:10.1007/s00774-022-01397-5

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

J Bone Miner Metab. 2023 Mar;41(2):212-219. doi: 10.1007/s00774-022-01397-5. Epub 2023 Jan 11.

Authors

Akemi Tokutsu¹, Yosuke Okada¹, Akira Kurozumi¹, Kenichi Tanaka¹, Satoshi Kubo¹, Yoshiya Tanaka²

Affiliations

¹ First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushyu-shi, Kitakyushu, 807-8555, Japan.
² First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushyu-shi, Kitakyushu, 807-8555, Japan. tanaka@med.uoeh-u.ac.jp.

PMID: 36629910
DOI: 10.1007/s00774-022-01397-5

Abstract

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.

Keywords: Activated Th17 cells; Chemotherapy; Cytokines; Flow cytometric analysis; IL-17; Langerhans cell histiocytosis (LCH).

Publication types

Case Reports

MeSH terms

Aged
CD4-Positive T-Lymphocytes / pathology
Female
Histiocytosis, Langerhans-Cell* / complications
Histiocytosis, Langerhans-Cell* / diagnosis
Histiocytosis, Langerhans-Cell* / pathology
Humans
Interleukin-17 / therapeutic use
Magnetic Resonance Imaging
Osteolysis*
Receptors, CXCR3
Receptors, CXCR6

Substances

Interleukin-17
CXCR6 protein, human
Receptors, CXCR6
CXCR3 protein, human
Receptors, CXCR3