TY - JOUR
T1 - NK cell expansion requires HuR and mediates control of solid tumors and long-term virus infection
AU - Piersma, Sytse J.
AU - Bangru, Sushant
AU - Yoon, Jeesang
AU - Liu, Tom W.
AU - Yang, Liping
AU - Hsieh, Chyi Song
AU - Plougastel-Douglas, Beatrice
AU - Kalsotra, Auinash
AU - Yokoyama, Wayne M.
N1 - Publisher Copyright:
© 2023 Piersma et al.
PY - 2023
Y1 - 2023
N2 - Natural killer (NK) cells are lymphocytes capable of controlling tumors and virus infections through direct lysis and cytokine production. While both T and NK cells expand and accumulate in affected tissues, the role of NK cell expansion in tumor and viral control is not well understood. Here, we show that posttranscriptional regulation by the RNA-binding protein HuR is essential for NK cell expansion without negatively affecting effector functions. HuR-deficient NK cells displayed defects in the metaphase of the cell cycle, including decreased expression and alternative splicing of Ska2, a component of the spindle and kinetochore complex. HuR-dependent NK cell expansion contributed to long-term cytomegalovirus control and facilitated control of subcutaneous tumors but not tumor metastases in two independent tumor models. These results show that posttranscriptional regulation by HuR specifically affects NK cell expansion, which is required for the control of long-term virus infection and solid tumors, but not acute infection or tumor metastases, highlighting fundamental differences with antigenspecific T cell control.
AB - Natural killer (NK) cells are lymphocytes capable of controlling tumors and virus infections through direct lysis and cytokine production. While both T and NK cells expand and accumulate in affected tissues, the role of NK cell expansion in tumor and viral control is not well understood. Here, we show that posttranscriptional regulation by the RNA-binding protein HuR is essential for NK cell expansion without negatively affecting effector functions. HuR-deficient NK cells displayed defects in the metaphase of the cell cycle, including decreased expression and alternative splicing of Ska2, a component of the spindle and kinetochore complex. HuR-dependent NK cell expansion contributed to long-term cytomegalovirus control and facilitated control of subcutaneous tumors but not tumor metastases in two independent tumor models. These results show that posttranscriptional regulation by HuR specifically affects NK cell expansion, which is required for the control of long-term virus infection and solid tumors, but not acute infection or tumor metastases, highlighting fundamental differences with antigenspecific T cell control.
UR - http://www.scopus.com/inward/record.url?scp=85170632442&partnerID=8YFLogxK
U2 - 10.1084/jem.20231154
DO - 10.1084/jem.20231154
M3 - Article
C2 - 37698554
AN - SCOPUS:85170632442
SN - 0022-1007
VL - 220
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 11
M1 - e20231154
ER -