Related Experiment Video
Updated: Oct 12, 2025
Induction of Intestinal Inflammation by Adoptive Transfer of CBir1 TCR Transgenic CD4+ T Cells to Immunodeficient Mice
Published on: December 16, 2021
Macrophages from gut-corrected CF mice express human CFTR and lack a pro-inflammatory phenotype
Jonathan L Gillan1, Gareth R Hardisty1, Donald J Davidson1
1Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
Abstract:
Macrophages represent prominent immune orchestrators of cystic fibrosis (CF) inflammation and, as such, are an ever-increasing focus of CF research with several reports of intrinsic immune dysfunction related to loss of CFTR activity in macrophages themselves. Animal models of CF have contributed, in no small part, to a deepening of our understanding of the pathophysiology of the disease and towards therapeutic development. A commonly-used animal model in CF research is the Cftrtm1Unc Tg(FABP-hCFTR) mouse, which displays gut-specific expression of a human CFTR transgene in order to rescue the high rate of early mortality in Cftr-null mice associated with severe intestinal obstruction. We find significant variation in the response to inflammatory challenge of patient macrophages and cells derived from the Cftrtm1Unc Tg(FABP-hCFTR) mouse and show that macrophages derived from this mouse exhibit aberrant expression of human CFTR. This may contribute to the absence of inflammatory changes in this model.
Insights
Macrophages play a key role in cystic fibrosis (CF) inflammation. This study found that a common CF mouse model exhibits aberrant human CFTR expression in macrophages, potentially explaining its lack of inflammatory response.
Area of Science:
- Immunology
- Genetics
- Cell Biology
Background:
- Macrophages are central to cystic fibrosis (CF) inflammation.
- CFTR dysfunction in macrophages contributes to CF pathophysiology.
- Animal models are crucial for understanding CF and developing therapies.
Purpose of the Study:
- To investigate macrophage inflammatory responses in CF.
- To evaluate the utility of the Cftrtm1Unc Tg(FABP-hCFTR) mouse model.
- To identify potential discrepancies between CF patient cells and the mouse model.
Main Methods:
- Cultured macrophages from CF patients and the Cftrtm1Unc Tg(FABP-hCFTR) mouse model.
- Inflammatory challenge assays.
- Analysis of human CFTR expression in macrophages.
Main Results:
- Significant variation observed in inflammatory responses between patient-derived and mouse-derived macrophages.
- Macrophages from the Cftrtm1Unc Tg(FABP-hCFTR) mouse model displayed aberrant human CFTR expression.
- This aberrant expression may account for the lack of expected inflammatory changes in the model.
Conclusions:
- The Cftrtm1Unc Tg(FABP-hCFTR) mouse model may not fully recapitulate CF macrophage inflammation due to aberrant human CFTR expression.
- Further research is needed to refine CF animal models for accurate immune response studies.
- Understanding macrophage dysfunction in CF is critical for targeted therapeutic strategies.
