Cd207(+)Cd1a(+) Cells Circulate In Pediatric Patients With Active Langerhans Cell Histiocytosis

Langerhans cell histiocytosis (LCH) is a rare disease with an unknown etiology characterized by heterogeneous lesions containing CD207(+)CD1a(+) cells that can arise in almost any tissue and cause significant morbidity and mortality. Precursors of pathological Langerhans cells have yet to be defined. Our aim was to identify circulating CD207(+)CD1a(+) cells and their inducers in LCH. Expression of CD207 and CD1a in the blood myeloid compartment as well as thymic stromal lymphopoietin (TSLP) and transforming growth factor beta (TGF-beta) plasma levels were measured in 22 pediatric patients with active disease (AD) or nonactive disease (NAD). In patients with AD vs those with NAD, the myeloid compartment showed an increased CD11b (CD11b(high) plus CD11b(+)) fraction (39.7 +/- 3.6 vs 18.6 +/- 1.9), a higher percentage of circulating CD11b(high)CD11c(+)CD207(+) cells (44.5 +/- 11.3 vs 3.2 +/- 0.5), and the presence of CD11c(high)CD207(+)CD1a(+) cells (25.0 +/- 9.1 vs 2.3 +/- 0.5). Blood CD207(+)CD1a(+) cells were not observed in adult controls or umbilical cord. Increased TSLP and TGF-beta levels were detecded in patients with AD. Interestingly, plasma from patients with AD induces CD207 expression on CD14(+) monocytes. We conclude that CD207(+)CD1a(+) cells are circulating in patients with active LCH, and TSLP and TGF-beta are potential drivers of Langerhans-like cells in vivo.