Fig. 4

Proposed role of MCPyV in the development of LCH. We propose LCH is a reactive disorder with underlying neoplastic potential using a triple-risk factor model. Infection usually triggers cytokine production and antibody production. However, MCPyV infection triggers cytokine storm including IL-1 and IL-6 in LCH patients. IL-1 and IL-6 stimulate IL-17 producing cells. We found IL-17A receptor expression levels in LCH cells are important for defining LCH subclasses. IL-17/IL-17 receptor signaling pathways include matrix metalloproteinase-3 (MMP3) or MMP12 which induce bone absorption. MCPyV: Merkel cell polyomavirus; LCH: Langerhans cell histiocytosis; LC: Langerhans cell; LCH cells: CD1a-positive activated Langerhans (not atypical Langerhans cell, morphologically)-like cells in LCH lesion