Figure 3

Proposed relationship between MCPyV and wild-type Langerhans cell (LC) precursors and wild-type LCs or mutated monocytes and mutated LC precursors. (A) MCPyV usually causes inapparent infection with immunoglobulin production against MCPyV, indicating acquired immunity against MCPyV is actuated by antigen presenting cells. LCs are antigen presenting cells derived from bone marrow (BM). LCs are normally generated and maintained locally in the steady state from precursors in the epidermis itself. In inflammation LC precursors are replenished by monocytes. Monocytes and LC precursors are candidate reservoir cells for MCPyV. (B) On the contrary, mutated precursor LCH cells (mutant monocytes, mutant LC precursors or mutant LCs) do not show inapparent infection against MCPyV; in such cases, a reactive disorder might be triggered, such as proliferation of LCH cells, cytokine storms including IL-1β, and clinical remissions. Mutated precursor LCH cells (mutant monocytes) in blood vessels recognize MCPyV and induce LCH-RO (+). Mutated LCH precursor cells (mutant LC precursors or mutant LCS) in peripheral tissues recognize MCPyV and induce LCH-RO (−). Most patients with LCH-RO (+) develop MS-LCH. Some patients with only one high-risk organ involved have a milder clinical course, similar to that observed in SS-LCH. In addition to IL-1 loop, serum level of IL-18 (one of IL-1 agonists) and osteopontin that is closely related to IL-1 levels were significantly higher in LCH-RO (+) than that found in LCH-RO (−).