MyD88, the myeloid differentiation primary response protein 88, is the canonical adaptor for inflammatory signaling pathways downstream of Toll-like receptor (TLR) and interleukin-1 (IL-1) receptor families. It links these receptors to IL-1R-associated kinase (IRAK) family kinases via homotypic protein-protein interaction, activating pathways like nuclear factor-kappa B (NFκB), mitogen-activated protein kinases, and activator protein 1, thus being a central node in inflammatory pathways [1].

In MyD88-KO mice, MPLA-induced resistance to Staphylococcus aureus infection is lost, indicating that MyD88-dependent signaling is critical in TLR-mediated trained immunity in macrophages [2]. Also, MyD88 deficiency in either quiescent or activated hepatic stellate cells (qHSCs or aHSCs) attenuates liver fibrosis in mice, inhibits α-SMA-positive cell activation, and decreases inflammatory cell infiltration and pro-inflammatory gene expression. MyD88 in HSCs promotes macrophage M1 polarization through CXCL10-CXCR3-JAK/STAT1 pathway, contributing to liver fibrosis [3]. In colorectal cancer, silencing MyD88 in SW480 and HCT116 cells suppresses growth, invasion, and affects the MyD88-NF-κB/AP-1 signaling pathways, and MyD88 knockdown inhibits tumor growth in a nude mouse model [4].

In conclusion, MyD88 is essential in innate immune and inflammatory signaling. Gene knockout mouse models have revealed its roles in diseases such as infections, liver fibrosis, and colorectal cancer. These findings highlight MyD88 as a potential therapeutic target in these disease areas, contributing to a better understanding of disease mechanisms and the development of new treatment strategies.