MyD88, myeloid differentiation primary response protein 88, is a canonical adaptor in innate immune signaling. It links IL-1 receptor (IL-1R) or Toll-like receptor (TLR) family members to IL-1R-associated kinase (IRAK) family kinases via protein-protein interaction, activating pathways like NFκB, mitogen-activated protein kinases, and activator protein 1, thus being a central node in inflammatory pathways [1].

MyD88-KO mice showed loss of MPLA-induced resistance to Staphylococcus aureus infection, indicating MyD88-dependent signaling is crucial in TLR-mediated trained immunity in macrophages [2]. In liver fibrosis models, MyD88 deficiency in quiescent or activated hepatic stellate cells (qHSCs or aHSCs) attenuated liver fibrosis, inhibited α-SMA-positive cell activation, and decreased pro-inflammatory gene expression [3]. In colorectal cancer, knockdown of MyD88 in cell lines and in a nude mouse model suppressed cell growth, invasion, and migration, affecting the MyD88-NF-κB/AP-1 signaling pathways [4].

In conclusion, MyD88 is essential in innate immune and inflammatory signaling. Gene knockout mouse models have revealed its roles in various disease conditions such as infectious diseases, liver fibrosis, and colorectal cancer, highlighting its potential as a therapeutic target in these areas.

References:

1. Deguine, Jacques, Barton, Gregory M. 2014. MyD88: a central player in innate immune signaling. In F1000prime reports, 6, 97. doi:10.12703/P6-97. https://pubmed.ncbi.nlm.nih.gov/25580251/

2. Owen, Allison M, Luan, Liming, Burelbach, Katherine R, Sherwood, Edward R, Bohannon, Julia K. 2022. MyD88-dependent signaling drives toll-like receptor-induced trained immunity in macrophages. In Frontiers in immunology, 13, 1044662. doi:10.3389/fimmu.2022.1044662. https://pubmed.ncbi.nlm.nih.gov/36439136/

3. Zhang, Jie, Liu, Yu, Chen, Haiqiang, Gu, Jianchun, Zhang, Jinhua. 2022. MyD88 in hepatic stellate cells enhances liver fibrosis via promoting macrophage M1 polarization. In Cell death & disease, 13, 411. doi:10.1038/s41419-022-04802-z. https://pubmed.ncbi.nlm.nih.gov/35484116/

4. Zhu, Guangwei, Cheng, Zhibin, Huang, Yongjian, Lin, Chunlin, Ye, Jianxin. 2019. MyD88 mediates colorectal cancer cell proliferation, migration and invasion via NF‑κB/AP‑1 signaling pathway. In International journal of molecular medicine, 45, 131-140. doi:10.3892/ijmm.2019.4390. https://pubmed.ncbi.nlm.nih.gov/31746347/