Refined cell transfer model reveals roles for Ascl2 and Cxcr3 in splenic localization of mouse NK cells during virus infection
Year: 2025
Type: article
Abstract: Cell transfer experiments complement the rigorous investigation of antiviral and antitumor functions of natural killer (NK) cells. Success in these endeavors is enhanced by expansion of small numbers of input NK cells driven by viral antigens or homeostatic proliferation in immunodeficient hosts. In contrast, analysis of other NK-cell functions, including immunoregulation, are non-proliferative and require an intact immune system in recipient mice. We reveal poor persistence of conventional congenic (CD45.1) BoyJ NK cells following adoptive transfer in comparison to CRISPR-generated CD45.1+ (JAXBoy) NK cells. Reciprocal transfers between C57BL/6 and JAXBoy mice substantially improve seeding and maintenance of donor NK cells. Using this system, we confirm that CXCR3 re-positions NK cells in the white pulp of the spleen after infection, which is vital for immunoregulation. Moreover, we discovered that the transcription factor ASCL2 is required for recruitment of NK cells into the spleen and white pulp. These results provide improved tools and novel insights into NK cell biology.
Source: The Journal of Immunology
Authors: Laura M Canaday, Andrew Cox, H Alex Feldman, Harsha Seelamneni, Ayad Ali, Jasmine A Tuazon, Lorena Botero Calderon, Sierra N Bennett, Allison Yan, Megan Wilson, Vijayakumar Velu, Stephen N Waggoner
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,500
Funders: Cincinnati Children's Hospital Medical Center, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Pathogenesis and therapeutic targeting of immune disorders, Targeting natural killer cells to enhance HIV vaccine responses, Medical Scientist Training Program, G7080086477, Transcription Factor Genetics in Lupus, Cincinnati Rheumatic Diseases Resource Center, Vaccinology Training Program, Digestive Health Center (DHC): Bench to Bedside Research in Pediatric Digestive Disease, Blocking granzyme-mediated immune suppression to enhance HIV vaccine efficacy, Cincinnati Children's Hospital Medical Center Vaccine and Treatment Evaluation Units (UM1 Clinical Trial Required), Pediatric Scientist Development Program, Leadership Group for the Infectious Diseases Clinical Research Consortium (IDCRCLG)
OpenAlex ID: W4412561115