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An IL-8 Transiently Transgenized Mouse Model for the In Vivo Long-term Monitoring of Inflammatory Responses
Published on: July 7, 2017
Modulation of innate immunity by IL-18
Wen Li1, Hideyuki Yamamoto, Shuji Kubo
1Hyogo College of Medicine, Laboratory of Host Defense, Institute for Medical Science, Mukogawa-cho, Nishinomiya, Japan.
Interleukin-18 (IL-18) promotes the expansion of gammadelta T cells, enhancing their anti-tumor activity. This cytokine plays a key role in immune responses and cell survival.
Area of Science:
- Immunology
- Cell Biology
- Reproductive Biology
Background:
- Interleukin-18 (IL-18) is expressed in reproductive organs, with fluctuating levels during the menstrual cycle, implantation, pregnancy, and delivery.
- The precise roles of IL-18 in reproduction are not fully understood, and its functions in immune and inflammatory responses are complex and sometimes paradoxical.
- IL-18 is known to activate anti-apoptotic signals, promoting the survival and proliferation of lymphocytes and other stressed cells.
Purpose of the Study:
- To investigate the role of IL-18 in the expansion and function of gammadelta T cells.
- To determine the impact of IL-18 on the phenotype and cytotoxic activity of expanded gammadelta T cells.
- To explore the potential of IL-18 in enhancing anti-tumor immunity.
Main Methods:
- Gammadelta T cells were stimulated with zoledronate and IL-2, with or without exogenous IL-18.
- Neutralizing anti-IL-18 receptor antibody was used to inhibit IL-18 signaling.
- Phenotypic analysis (CD44, CD27, CD45RA, NKG2D, perforin, CD94, CD25, CD122, CD56) and cytotoxicity assays against tumor cells were performed.
- Cytokine production (GM-CSF, IFNgamma, TNFalpha) by expanded gammadelta T cells was measured.
Main Results:
- Exogenous IL-18 significantly promoted the expansion of gammadelta T cells, an effect inhibited by anti-IL-18 receptor antibody.
- Expanded gammadelta T cells exhibited an effector memory phenotype (CD44+ CD27- CD45RA-) and expressed cytotoxic markers.
- These IL-18-expanded gammadelta T cells demonstrated potent cytotoxicity against tumor cells and inhibited tumor xenograft growth in mice.
- IL-18 induced higher production of GM-CSF, IFNgamma, and TNFalpha in expanded gammadelta T cells.
Conclusions:
- IL-18 effectively promotes the expansion of gammadelta T cells with enhanced cytotoxic potential.
- IL-18 may serve as a therapeutic agent to boost anti-tumor immunity through gammadelta T cell activation.
- Further research into IL-18's reproductive roles and its immunomodulatory functions is warranted.
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