found that TLR7 (mainly located on M2 in the IgG4-RD affected tissues) activation in vitro lead to enhanced interleukin 33 (IL-33) production by M2, which was also confirmed by the finding that human Toll-like receptor 7 (huTLR7)-transgenic C57BL/6 mice had severer tissue fibrosis after receiving the treatment of resiquimod (R848) (12). This evidence concerns the gene IL33 and immunoglobulin G4-related sclerosing disease.