Journal
FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.652786
Keywords
NF-κ B c-Rel; granzyme; perforin (Prf1); NK cell; cytotoxicity
Categories
Funding
- Athymic Animal and Hemapoietic Biorepository and Cellular therapy core facilities, Shared Resources of the Case Comprehensive Cancer Center [P30CA043703]
Ask authors/readers for more resources
Germline deficiency of NF-kappa B c-Rel leads to a marked decrease in cytotoxic function of NK cells, which is regulated by c-Rel through controlling the expression of perforin and granzyme B. The study reveals a crucial role of c-Rel in the cytotoxic function of NK cells through transcriptional regulation of perforin and granzyme B expressions.
Natural Killer (NK) cells are cytotoxic lymphocytes critical to the innate immune system. We found that germline deficiency of NF-kappa B c-Rel results in a marked decrease in cytotoxic function of NK cells, both in vitro and in vivo, with no significant differences in the stages of NK cell development. We found that c-Rel binds to the promoters of perforin and granzyme B, two key proteins required for NK cytotoxicity, and controls their expression. We generated a NK cell specific c-Rel conditional knockout to study NK cell intrinsic role of c- Rel and found that both global and conditional c-Rel deficiency leads to decreased perforin and granzyme B expression and thereby cytotoxic function. We also confirmed the role of c-Rel in perforin and granzyme B expression in human NK cells. c-Rel reconstitution rescued perforin and granzyme B expressions in c-Rel deficient NK cells and restored their cytotoxic function. Our results show a previously unknown role of c-Rel in transcriptional regulation of perforin and granzyme B expressions and control of NK cell cytotoxic function.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available