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20220088
Cell-specific gene expression in Langerhans cell histiocytosis lesions reveals a distinct profile compared with epidermal Langerhans cells.

J Immunol, 2010/4/15;184(8):4557-67.

Allen CE[1], Li L, Peters TL, Leung HC, Yu A, Man TK, Gurusiddappa S, Phillips MT, Hicks MJ, Gaikwad A, Merad M, McClain KL

Affiliations

PMID: 20220088DOI: 10.4049/jimmunol.0902336

Impact factor: 5.426

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.
MeSH terms
Adolescent; Antigens, CD; Biomarkers; CD3 Complex; Child; Child, Preschool; Epidermal Cells; Epidermis; Gene Expression Profiling; Histiocytosis, Langerhans-Cell; Humans; Infant; Langerhans Cells; Lectins, C-Type; Mannose-Binding Lectins; Oligonucleotide Array Sequence Analysis
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