In:
Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-4-29)
Abstract:
Natural Killer (NK) cells are cytotoxic lymphocytes critical to the innate immune system. We found that germline deficiency of NF-κB 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.
Type of Medium:
Online Resource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2021.652786
DOI:
10.3389/fimmu.2021.652786.s001
DOI:
10.3389/fimmu.2021.652786.s002
DOI:
10.3389/fimmu.2021.652786.s003
DOI:
10.3389/fimmu.2021.652786.s004
DOI:
10.3389/fimmu.2021.652786.s005
DOI:
10.3389/fimmu.2021.652786.s006
DOI:
10.3389/fimmu.2021.652786.s007
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2021
detail.hit.zdb_id:
2606827-8
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