| First Author | Vicioso Y | Year | 2021 |
| Journal | Front Immunol | Volume | 12 |
| Pages | 652786 | PubMed ID | 33995369 |
| Mgi Jnum | J:341834 | Mgi Id | MGI:6741946 |
| Doi | 10.3389/fimmu.2021.652786 | Citation | Vicioso Y, et al. (2021) NF-kappaB c-Rel Is Dispensable for the Development but Is Required for the Cytotoxic Function of NK Cells. Front Immunol 12:652786 |
| abstractText | Natural Killer (NK) cells are cytotoxic lymphocytes critical to the innate immune system. We found that germline deficiency of NF-kappaB 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. |
