IFN-λ therapy prevents severe gastrointestinal graft-versus-host disease.

Immunopathology and intestinal stem cell (ISC) loss in the gastrointestinal (GI) tract is the prima facie manifestation of graft-versus-host disease (GVHD) and is responsible for significant mortality after allogeneic bone marrow transplantation (BMT). Approaches to prevent GVHD to date focus on immune suppression. Here, we identify interferon-λ (IFN-λ; interleukin-28 [IL-28]/IL-29) as a key protector of GI GVHD immunopathology, notably within the ISC compartment. Ifnlr1-/- mice displayed exaggerated GI GVHD and mortality independent of Paneth cells and alterations to the microbiome. Ifnlr1-/- intestinal organoid growth was significantly impaired, and targeted Ifnlr1 deficiency exhibited effects intrinsic to recipient Lgr5+ ISCs and natural killer cells. PEGylated recombinant IL-29 (PEG-rIL-29) treatment of naive mice enhanced Lgr5+ ISC numbers and organoid growth independent of both IL-22 and type I IFN and modulated proliferative and apoptosis gene sets in Lgr5+ ISCs. PEG-rIL-29 treatment improved survival, reduced GVHD severity, and enhanced epithelial proliferation and ISC-derived organoid growth after BMT. The preservation of ISC numbers in response to PEG-rIL-29 after BMT occurred both in the presence and absence of IFN-λ-signaling in recipient natural killer cells. IFN-λ is therefore an attractive and rapidly testable approach to prevent ISC loss and immunopathology during GVHD.

Quantitative analysis of fetal magnetic resonance phantoms and recommendations for an anthropomorphic motion phantom.

OBJECTIVE: To provide a review and quantitative analysis of the available fetal MR imaging phantoms. MATERIALS AND METHODS: A literature search was conducted across Pubmed, Google Scholar, and Ryerson University Library databases to identify fetal MR imaging phantoms. Phantoms were graded on a semi-quantitative scale in regards to four evaluation categories: (1) anatomical accuracy in size and shape, (2) dielectric conductivity similar to the simulated tissue, (3) relaxation times similar to simulated tissue, and (4) physiological motion similar to fetal gross body, cardiovascular, and breathing motion. This was followed by statistical analysis to identify significant findings. RESULTS: Seventeen fetal phantoms were identified and had an average overall percentage accuracy of 26%, with anatomical accuracy being satisfied the most (56%) and physiological motion the least (7%). Phantoms constructed using 3D printing were significantly more accurate than conventionally constructed phantoms. DISCUSSION: Currently available fetal phantoms lack accuracy and motion simulation. 3D printing may lead to higher accuracy compared with traditional manufacturing. Future research needs to focus on properly simulating both fetal anatomy and physiological motion to produce a phantom that is appropriate for fetal MRI sequence development and optimization.