Codan, C. | Search bioRxiv

bioRxiv2026

Medical diagnostic radiation promotes murine Apc/Kras-driven colon carcinogenesis

Computed tomography (CT) is one of the most widely used diagnostic imaging modalities worldwide, yet the biological risks associated with such exposures remain incompletely understood. Here, we investigated the effects of clinically relevant low (25 mGy) and moderate (250 mGy) dose radiation exposures on colon carcinogenesis using in vivo KPC:APC transgenic mice and an ex vivo organoid system carrying inducible Apc and Kras driver mutations. While medical diagnostic radiation did not initiate carcinogenesis in wild-type and did not alter carcinogenesis in Apc-mutant tissues, it significantly promoted the progression of precancerous lesions in the presence of both mutations, especially when exposure occurred during early tumor initiation. Organoids derived from mice harboring both Apc and Kras mutations mirrored this susceptibility, exhibiting radiation-induced enlargement and activation of transcriptomic and proteomic programs associated with colorectal cancer, including cell-cycle dysregulation and mTORC1 pathway activation. These findings show that radiation doses within the range delivered by routine abdominal CT imaging can potentiate the carcinogenic processes in genetically predisposed cells, underscoring the need to consider individual susceptibility when evaluating the benefit-risk balance of medical diagnostic exposures.

Cancer Biology↗

bioRxiv2024

Adaptive immunity shapes innate and epithelial cell landscapes by silencing tonic IFN-gamma in innate lymphoid cells during homeostasis.

During homeostasis, innate and epithelial cells undergo continuous maturation, shaped by microbial, molecular and cellular interactions. While these cells influence adaptive immunity during steady-state conditions, the reciprocal homeostatic role of adaptive immune cells in the maturation and function of innate and epithelial cells remains underexplored. Here, through computational approaches and murine models, we establish that adaptive immunity shapes innate immune and epithelial homeostatic landscapes. Mechanistically, adaptive immunity acts as a brake on type 1 polarization and diversification of innate lymphocytes (ILCs). Without adaptive immunity, the innate cellular interactions within the mesenteric lymph nodes are dominated by an interferon-gamma (IFN{gamma}) signaling network. Moreover, the innate immune and epithelial cells follow distinct phenotypic and functional trajectories, including ILCs acquiring myeloid markers, monocytes adopting an inflammatory path, and colonic epithelial cells expressing altered antimicrobial peptides and losing Paneth-like features. Depleting ILCs, abolishing IFN{gamma} signaling, or restoring adaptive immunity reduces these IFN{gamma}-driven changes. Thus, our findings highlight a homeostatic function of adaptive immunity in modulating innate and epithelial cell communication, diversity, composition, function, and differentiation, notably by limiting ILC-derived IFN{gamma}.

immunology↗