| First Author | Kaur K | Year | 2022 |
| Journal | Cell Immunol | Volume | 375 |
| Pages | 104526 | PubMed ID | 35500335 |
| Mgi Jnum | J:325657 | Mgi Id | MGI:7280501 |
| Doi | 10.1016/j.cellimm.2022.104526 | Citation | Kaur K, et al. (2022) Zoledronic acid mediated differential activation of NK cells in different organs of WT and Rag2(-/-) mice; stark differences between the bone marrow and gingivae. Cell Immunol 375:104526 |
| abstractText | We have previously shown that natural killer (NK) cells expand, and increase their function after interaction with cells that exhibit a number of different knock-down genes. We hypothesized that deletion or knockdown of a variety of key genes such as RAG may cause de-differentiation of the cells which could lead to increased NK expansion and function since we have shown previously that NK cells are activated and expanded by less differentiated cells. When comparing the function of NK cells from bone marrow (BM), spleen, pancreas, adipose tissue, and gingiva from WT mice to those from Rag2(-/-) mice, we observed a significant increase in IFN-gamma secretion in all tissues of Rag2(-/-) mice versus in WT mice, with the exception of the gingivae in which similar levels were observed. After injecting WT mice with zoledronic acid (ZOL) and tooth extraction, immune cells from BM, spleen, and purified NK cells from spleen exhibited very high induction of IFN-gamma and NK cell-mediated cytotoxicity with the exception of gingiva in which immune cells exhibited the opposite. In Rag2(-/-) mice, ZOL injection and tooth extraction stimulated IFN-gamma secretion from BM immune cells but inhibited IFN-gamma secretion from both spleen and gingivae. In both WT and Rag2(-/-) mice, immune cells from gingivae exhibited decreased IFN-gamma secretion when activated, indicating significant regulation of immune cell function in the gingival microenvironment. However, even though significantly lower induction of IFN-gamma was observed in both WT and Rag2(-/-) gingival cells after ZOL injection, ZOL mediated secretion of IFN-gamma was still higher in the gingivae of WT mice when compared to those of Rag2(-/-) gingival cells. These results suggest an important role for IFN-gamma in the pathogenesis of osteonecrosis lesions observed in post-tooth extraction jawbone. |
