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Eosinophils are present in the thymus of mammals, yet their function at this site during homeostatic development is unknown. We used flow cytometry to determine the abundance and phenotype of eosinophils (here defined as SSchigh SiglecF+ CD11b+ CD45+ cells) in the thymus of mice during the neonatal period, the later postnatal period, and into adulthood. We show that both the total number of thymic eosinophils and their frequency among leukocytes increase over the first 2 wk of life and that their accumulation in the thymus is dependent on the presence of an intact bacterial microbiota. We report that thymic eosinophils express the interleukin-5 receptor (CD125), CD80, and IDO, and that subsets of thymic eosinophils express CD11c and major histocompatibility complex II (MHCII). We found that the frequency of MHCII-expressing thymic eosinophils increases over the first 2 wk of life, and that during this early-life period the highest frequency of MHCII-expressing thymic eosinophils is located in the inner medullary region. These data suggest a temporal and microbiota-dependent regulation of eosinophil abundance and functional capabilities in the thymus. [ABSTRACT FROM AUTHOR]

Objective: One of the major issues in current radiotherapy (RT) is the normal tissue toxicity. A smart combination of agents within the tumor would allow lowering the RT dose required while minimizing the damage to healthy tissue surrounding the tumor. We chose gold nanoparticles (GNPs) and docetaxel (DTX) as our choice of two radiosensitizing agents. They have a different mechanism of action which could lead to a synergistic effect. Our first goal was to assess the variation in GNP uptake, distribution, and retention in the presence of DTX. Our second goal was to assess the therapeutic results of the triple combination, RT/GNPs/DTX. Methods: We used HeLa and MDA-MB- 231 cells for our study. Cells were incubated with GNPs (0.2 nM) in the absence and presence of DTX (50 nM) for 24 h to determine uptake, distribution, and retention of NPs. For RT experiments, treated cells were given a 2 Gy dose of 6 MV photons using a linear accelerator. Results: Concurrent treatment of DTX and GNPs resulted in over 85% retention of GNPs in tumor cells. DTX treatment also forced GNPs to be closer to the most important target, the nucleus, resulting in a decrease in cell survival and increase in DNA damage with the triple combination of RT/ GNPs/DTX vs RT/DTX. Our experimental therapeutic results were supported by Monte Carlo simulations. Conclusion: The ability to not only trap GNPs at clinically feasible doses but also to retain them within the cells could lead to meaningful fractionated treatments in future combined cancer therapy. Furthermore, the suggested triple combination of RT/GNPs/DTX may allow lowering the RT dose to spare surrounding healthy tissue. Advances in knowledge: This is the first study to show intracellular GNP transport disruption by DTX, and its advantage in radiosensitization. [ABSTRACT FROM AUTHOR]