Metabolic syndrome is a major risk factor of cardiovascular events, and adipose tissue obesity based on chronic inflammation play a central role. To assess dynamic interplay between multiple cell-types in inflammatory diseases, in vivo imaging technique based on single- and multi-photon microscopy was developed. Imaging revealed close spatial and temporal interrelationships between angiogenesis and adipogenesis in obese adipose. In addition, increased leukocyte-platelet-endotheliel cell interactions in the microcirculation of obese adipose were observed, a hallmark of inflammation. We also found that large numbers of CD8+ effector T cells infiltrated into obese adipose. Infiltration by CD8+ T cells is essential for the initiation and development of adipose inflammation. By our in vivo imaging technique, multiple cell types are specifically visualized, and thrombus formation was induced by laser irradiation which cause ROS production inside the blood vessel. Using this technique, we revealed Lnk/Sh2b3 regulates integrin alpha-IIb-beta-3 outside-in signaling in platelets leading to stabilization of developing thrombus in vivo. In addition, we established human iPS-derived platelets, and tracked them in mice to elucidate its function in vivo. We confirmed injected platelets circulate, and contributed to the thrombus formation in vivo, indicating the clinical usefulness of this strategy for future. Our results clearly demonstrated the power of our imaging technique to analyze complex cellular interplays in inflammatory diseases, especially parenchymal and stromal cell cross talks, and to evaluate new therapeutic interventions against them.

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