The transcriptional programme of natural killer (NK) cell functional maturation and maintenance

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. The functional maturation of NK cells is a tightly regulated process which is controlled by transcription factors (TFs), and multiple positive regulators of this process have been defined. However, 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. The studies presented here 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 tonic IL-15 signalling. Loss of BACH2 within NK cells results in accumulation of activated NK cells with unrestrained cytotoxic function and increased immune surveillance to pulmonary cancer metastasis. These findings establish a critical function of BACH2 as a negative regulator of innate cytotoxic function and tumour immune surveillance by NK cells.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2022

Author dc:creator

• Imianowski, Charlotte

Advisor dc:contributor.advisor

• Roychoudhuri, Rahul

• Natural Killer cells
• Innate lymphocytes
• Anti-tumour immunity
• Immune surveillance
• Transcriptional regulation
• Transcription factor
• BACH2

Licence

• http://purl.org/NET/rdflicense/allrightsreserved

Language dc:language

eng

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.87802

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/340364