Zoledronic acid mediated differential activation of NK cells in different organs of WT and Rag2(-/-) mice; stark differences between the bone marrow and gingivae

作者全名："Kaur, Kawaljit; Kanayama, Keiichi; Wu, Qing-Qing; Gumrukcu, Serhat; Nishimura, Ichiro; Jewett, Anahid"

作者地址："[Kaur, Kawaljit; Jewett, Anahid] Univ Calif Los Angeles, Div Oral Biol & Med, Sch Dent, 10833 Le Conte Ave, Los Angeles, CA 90095 USA; [Kaur, Kawaljit; Kanayama, Keiichi; Wu, Qing-Qing; Nishimura, Ichiro; Jewett, Anahid] UCLA, Weintraub Ctr Reconstruct Biotechnol, Sch Dent, Los Angeles, CA 90095 USA; [Kanayama, Keiichi] Asahi Univ, Dept Periodontol, Sch Dent, Gifu 5010296, Japan; [Wu, Qing-Qing] Chongqing Med Univ, Stomatol Hosp, Dept Oral Implantol, Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing 400015, Peoples R China; [Gumrukcu, Serhat] Seraph Res Inst, 2080 Century Pk East,Suite 710, Los Angeles, CA 90067 USA"

通信作者："Jewett, A (通讯作者)，Univ Calif Los Angeles, Div Oral Biol & Med, Sch Dent, 10833 Le Conte Ave, Los Angeles, CA 90095 USA.; Nishimura, I; Jewett, A (通讯作者)，UCLA, Weintraub Ctr Reconstruct Biotechnol, Sch Dent, Los Angeles, CA 90095 USA."

来源：CELLULAR IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000804062800005

JCR分区：Q3

影响因子：4.3

年份：2022

卷号：375

期号：　

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结束页：　

文献类型：Article

关键词：NK cells; IFN-gamma; Cytotoxicity; Bone remodeling; Osteoclasts; Rag(2-/-)

摘要："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."

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