Figure 8

Proposed IL-1-loop model in LCH as a reactive disorder triggered by MCPyV. MyD88 is an adaptor of IL-1R and binds to pERK, maintaining ERK in an active, phosphorylated state. MyD88 also allows the activation of NF-κB, leading to the activation of further inflammatory and mitogenic signals. Induction of this IL-1β autocrine loop after MCPyV infection may lead to enhanced cell activation, proliferation, and eventually, transformation of LCH. In absence of MCPyV infection, the IL-1β paracrine loop also leads to enhanced cell activation, proliferation, and eventually, accumulation and cell survival of LCH cells. The clinical course of LCH may also be influenced by anti-inflammatory cytokines produced by T-cells under different conditions, including innate immunity alone and actuated acquired immunity against MCPyV.