IRAK4 and immunoglobulin G4-related sclerosing disease: In IgG4-related disease (IgG4-RD), CD163+ M2 Mφs promote fibroblast activation and fibrosis by releasing profibrotic cytokines (e.g., IL-33, TGF-β) through the TLR7/IRAK4/NF-κB pathway (56).