BACH2 restricts NK cell maturation and function, limiting immunity to cancer metastasis

Imianowski, C.J. (Charlotte J.); Whiteside, T.L. (Theresa L.); Lozano-Moreda, T. (Teresa); Evans, A.C. (Alexander C.); Benson, J.D. (Jayme D.); Courreges, C.J.F. (Christina J.F.); Sadiyah, F. (Firas); Lau, C.M. (Colleen M.); Zandhuis, N.D. (Nordin D.); Grant, F.M. (Francis M.); Schuijs, M.J. (Martijn J.); Vardaka, P. (Panagiota); Kuo, P. (Paula); Soilleux, E.J. (Elizabeth J.); Yang, J. (Jie); Sun, J.C. (Joseph C.); Kurosaki, T. (Tomohiro); Okkenhaug, K. (Klaus); Halim, T.Y.F. (Timotheus Y.F.); Roychoudhuri, R. (Rahul)

Keywords:

Materias Investigacion::Ciencias de la Salud
Innate immunity and inflammation
Tumor immunology

Issue Date:

2022

Publisher:

Rockefeller University Press

ISSN:

0022-1007

Note:

Available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license

Citation:

Imianowski, C.J. (Charlotte J.); Whiteside, T.L. (Theresa L.); Lozano-Moreda, T. (Teresa); et al. "BACH2 restricts NK cell maturation and function, limiting immunity to cancer metastasis". The Journal of Experimental Medicine. 219 (12), 2022, e20211476

Abstract

Natural killer (NK) cells are critical to immune surveillance against infections and cancer. Their role in immune surveillance requires that NK cells are present within tissues in a quiescent state. Mechanisms by which NK cells remain quiescent in tissues are incompletely elucidated. The transcriptional repressor BACH2 plays a critical role within the adaptive immune system, but its function within innate lymphocytes has been unclear. Here, we show that BACH2 acts as an intrinsic negative regulator of NK cell maturation and function. BACH2 is expressed within developing and mature NK cells and promotes the maintenance of immature NK cells by restricting their maturation in the presence of weak stimulatory signals. Loss of BACH2 within NK cells results in accumulation of activated NK cells with unrestrained cytotoxic function within tissues, which mediate augmented immune surveillance to pulmonary cancer metastasis. These findings establish a critical function of BACH2 as a global negative regulator of innate cytotoxic function and tumor immune surveillance by NK cells.

URI:

https://hdl.handle.net/10171/69307

DOI:

10.1084/jem.20211476

Appears in Collections:

DA - CIMA - Inmunología e Inmunoterapia - Inmunología hepatitis virales - Artículos de revista

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