# Refined cell transfer model reveals roles for Ascl2 and Cxcr3 in splenic localization of mouse NK cells during virus infection

## TL;DR

Researchers improved a cell transfer model to study how NK cells position themselves in the spleen during viral infections, revealing the roles of ASCL2 and CXCR3.

## Contribution

A refined cell transfer model using CRISPR-generated NK cells and identification of ASCL2 and CXCR3 roles in NK cell localization.

## Key findings

- CRISPR-generated JAXBoy NK cells persist better in recipients than conventional CD45.1 BoyJ NK cells.
- CXCR3 repositions NK cells in the spleen's white pulp after infection, aiding immunoregulation.
- ASCL2 is essential for recruiting NK cells into the spleen and white pulp.

## 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.

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