Cell-specific gene expression in Langerhans cell histiocytosis lesions reveals a distinct profile compared with epidermal Langerhans cells.

Abstract

Langerhans cell histiocytosis (LCH) is a rare disease characterized by heterogeneous lesions containing CD207(+) Langerhans cells (LCs) and lymphocytes that can arise in almost any tissue and cause significant morbidity and mortality. After decades of research, the cause of LCH remains speculative. A prevailing model suggests that LCH arises from malignant transformation and metastasis of epidermal LCs. In this study, CD207(+) cells and CD3(+) T cells were isolated from LCH lesions to determine cell-specific gene expression. Compared with control epidermal CD207(+) cells, the LCH CD207(+) cells yielded 2113 differentially expressed genes (false discovery rate < 0.01). Surprisingly, the expression of many genes previously associated with LCH, including cell-cycle regulators, proinflammatory cytokines, and chemokines, were not significantly different from control LCs in our study. However, several novel genes whose products activate and recruit T cells to sites of inflammation, including SPP1 (osteopontin), were highly overexpressed in LCH CD207(+) cells. Furthermore, several genes associated with immature myeloid dendritic cells were overexpressed in LCH CD207(+) cells. Compared with the peripheral CD3(+) cells from LCH patients, the LCH lesion CD3(+) cells yielded only 162 differentially regulated genes (false discovery rate < 0.01), and the expression profile of the LCH lesion CD3(+) cells was consistent with an activated regulatory T cell phenotype with increased expression of FOXP3, CTLA4, and SPP1. Results from this study support a model of LCH pathogenesis in which lesions do not arise from epidermal LCs but from accumulation of bone marrow-derived immature myeloid dendritic cells that recruit activated lymphocytes.

• Authors: Carl E Allen, Liunan Li, Tricia L Peters, Hon-Chiu Eastwood Leung, Alexander Yu, Tsz-Kwong Man, Sivashankarappa Gurusiddappa, Michelle T Phillips, M John Hicks, Amos Gaikwad, Miriam Merad, Kenneth L McClain
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 184 Issue 8 Pg. 4557-67 (Apr 15 2010) ISSN: 1550-6606 [Electronic] United States
• PMID: 20220088 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Biomarkers
• CD207 protein, human
• CD3 Complex
• Lectins, C-Type
• Mannose-Binding Lectins

Topics

• Adolescent
• Antigens, CD (biosynthesis, genetics)
• Biomarkers (metabolism)
• CD3 Complex (biosynthesis, genetics)
• Child
• Child, Preschool
• Epidermal Cells
• Epidermis (immunology, pathology)
• Gene Expression Profiling (methods)
• Histiocytosis, Langerhans-Cell (genetics, immunology, pathology)
• Humans
• Infant
• Langerhans Cells (cytology, immunology, pathology)
• Lectins, C-Type (biosynthesis, genetics)
• Mannose-Binding Lectins (biosynthesis, genetics)
• Oligonucleotide Array Sequence Analysis