Development of a humanized mouse model with functional human materno-fetal interface immunity

Area of Science:

• Immunology
• Reproductive Biology
• Transplantation Immunology

Background:

• Human materno-fetal immunity is crucial for pregnancy success but poorly understood due to limitations of animal models.
• Rodent models do not fully recapitulate human immunological processes at the materno-fetal interface.
• A need exists for a humanized model to accurately study pregnancy immunology.

Purpose of the Study:

• To develop and validate a pregnant human immune system (HIS) mouse model.
• To investigate the dynamic changes in human materno-fetal immunity during gestation.
• To identify cellular and molecular mechanisms governing immune tolerance and inflammation in pregnancy.

Main Methods:

• Development of a pregnant HIS mouse model using busulfan preconditioning.
• Analysis of immune cell populations and their interactions at the materno-fetal interface using single-cell RNA-Seq.
• Functional assessment of regulatory T (Treg) cells in maintaining pregnancy.

Main Results:

• The HIS mouse model successfully reconstitutes human immune subsets at the materno-fetal interface.
• Human materno-fetal immunity shifts from tolerogenic (mid-gestation) to inflammatory (late-gestation) profiles.
• Macrophages play a key role in regulating the immune environment, and Treg cell depletion causes inflammation and fetus rejection.

Conclusions:

• The pregnant HIS mouse model provides a valuable platform for studying human materno-fetal immunity.
• This model elucidates the dynamic immune changes during human pregnancy.
• Findings facilitate the development of therapeutic strategies for pregnancy complications and reproductive disorders.