Characterization of human lung immune cells in the humanized BRGSF mouse model

Pokhreal D
University of Paris
October 23, 2025
J Immunol
https://pubmed.ncbi.nlm.nih.gov/41129297/

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/41129297/

Research summary

Using human lung biopsies as reference, the study assessed lung immune cell composition in humanized BRGSF‑HIS mice engrafted with human CD34⁺ hematopoietic stem cells. They found human NK cells, CD4⁺ and CD8⁺ T cells, γδ T cells, regulatory T cells, monocytes and dendritic cells in the lung interstitium at frequencies comparable to human lungs. Mouse‑origin alveolar macrophages dominated alveoli. Exogenous human G‑CSF promoted egress of human CD15⁺ neutrophils. Human T cells responded to CD3 stimulation and myeloid cells secreted human cytokines (IL‑6, CCL17, IL‑10, IL‑1RA) upon LPS challenge.

Key outcome of the study

Humanized BRGSF mice display functional human lymphoid and myeloid lung‑resident cells in interstitium; human neutrophil egress inducible by hG‑CSF, human T cells and myeloid cells from lung are functionally responsive in vitro and in vivo

Model

genO-BRGSF-HIS humanized mouse, reconstituted with human CD34⁺ HSCs — genOway-developed

TARGET:
Not applicable
Synonyms:
Not applicable

Keywords

Lung immune modeling, humanized mice, lung interstitial immunity, human CD34⁺ engraftment, translational immunology

Technical specifications

CD34⁺ human HSC engraftment into BRGSF mice, lung tissue immunophenotyping, neutrophil mobilization via hG‑CSF, T cell stimulation assays, myeloid cytokine secretion assays

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