CD207+/CD1A+ CIRCULATING CELLS SHOW HIGHER LEVELS OF TYRO3, MERTK, AND PROS1 IN PATIENTS WITH ACTIVE LANGERHANS CELL HISTIOCYTOSIS

ROSSO, DIEGO A.; OLEXEN CINTHIA M; NOWAK W; ERRASTI ANDREA E; CARRERA SILVA EA

Memphis

Congreso; 35th Annual Meeting of the Histiocyte Society; 2019

Histiocyte Society

TYRO3, AXL and MERTK (TAM) tyrosine kinase receptors and its agonist Protein S (PROS1) have been identified as negative regulators of the immune response, as well as non-classical proto-oncogenes aberrantly expressed in hematological and epithelial malignancies. Langerhans Cell Histiocytosis (LCH) is a disorder characterized by an abnormal accumulation of CD207+CD1a+ myeloid cells in almost any tissue. The etiology of this disease is not completely understood and it is not clear if LCH results from malignant transformation, unbalanced immune response or both. Our aim was to determine the role of TAM axis in the pathogenesis of LCH in pediatric patients. Therefore, the expression of TAM receptors and PROS1 were measured in CD207+ and CD1a+ circulating cells gated in three myeloid fractions CD11bHighCD11cHigh, CD11bHighCD11cLow and CD11bLowCD11cLow from peripheral blood mononuclear cells of patients with active disease (AD), and compared with non-active disease (NAD) and adult controls by flow cytometry. All data is expressed as fold increase of mean fluorescence intensity referred to NAD and controls. We observed that CD207+ and CD1a+ cells showed higher expression levels of PROS1 and MERTK in the three myeloid populations of AD patients compared with NAD and adult controls. PROS1 was significantly higher in CD11bLowCD11cLow (~4.26-fold N=8); and MERTK in the three populations with an average of 4.8- fold (N=8). TYRO3 was significantly up-regulated in CD1a+ cells of the three fractions of AD donors with an average of 2.18-fold (N=8). Remarkable, we found that CD207+ or CD1a+ cells present in AD showed significantly higher levels of TYRO3, MERTK and PROS1 versus their own negative CD207/ CD1a population. Our results indicate that higher levels of TYRO3, MERTK and PROS1 are associated with active LCH and the presence of CD207 and CD1a markers, suggesting that TAM axis could be involved in the expansion of precursor of/or pathological LC-like cells.