A more human mouse

Nat. Meth. https://doi.org/10.1038/s41592-018-0071-6 (2018)

Humanized mice can address questions not readily amenable to other experimental models, but they lack proper development of secondary lymphoid tissue (SLT) with severely compromised adaptive immunity. In Nature Methods, Di Santo and colleagues backcross humanized BALB/c Rag2^–/–Il2rg^–/–Sirpa^NOD mice (‘BRGS mice’) to mice overexpressing the cytokine TSLP, generating ‘BRGST mice’. SLT development is dependent on the function of LTi cells, and the absence of the common γ-chain in BRGS mice means LTi cells fail to develop. However, high TSLP expression in BRGST mice restores LTi cell development and almost completely restores SLT and robust B cell and T cell function. BRGST mice might be a more powerful tool for investigating the human immune system.