| First Author | Aryee KE | Year | 2023 |
| Journal | J Leukoc Biol | Volume | 113 |
| Issue | 5 | Pages | 418-433 |
| PubMed ID | 36801998 | Mgi Jnum | J:335726 |
| Mgi Id | MGI:7469783 | Doi | 10.1093/jleuko/qiac020 |
| Citation | Aryee KE, et al. (2023) NOD-scid IL2rgammanull mice lacking TLR4 support human immune system development and the study of human-specific innate immunity. J Leukoc Biol 113(5):418-433 |
| abstractText | Agents that induce inflammation have been used since the 18th century for the treatment of cancer. The inflammation induced by agents such as Toll-like receptor agonists is thought to stimulate tumor-specific immunity in patients and augment control of tumor burden. While NOD-scid IL2rgammanull mice lack murine adaptive immunity (T cells and B cells), these mice maintain a residual murine innate immune system that responds to Toll-like receptor agonists. Here we describe a novel NOD-scid IL2rgammanull mouse lacking murine TLR4 that fails to respond to lipopolysaccharide. NSG-Tlr4null mice support human immune system engraftment and enable the study of human-specific responses to TLR4 agonists in the absence of the confounding effects of a murine response. Our data demonstrate that specific stimulation of TLR4 activates human innate immune systems and delays the growth kinetics of a human patient-derived xenograft melanoma tumor. |
