By showing that anti-inflammatory regulatory T cells (Tregs) move to and from the skin whilst regulating an immune response, an international research team involving RIKEN researchers has provided insight into how immune cells behave during inflammation.
The team, including Michio Tomura, Shohei Hori and Osami Kanagawa from the RIKEN Research Center for Allergy and Immunology in Yokohama and Kenji Kabashima from the Kyoto University Graduate School of Medicine, used a specially engineered line of mice to track immune cells in a living animal model. The mice—developed previously by Tomura, Kanagawa and colleagues—express a protein called Kaede that usually causes their cells to glow green, but glow red once exposed to violet light. This color switching allowed the researchers to tag cells from one part of the body and track them as they moved elsewhere. “This kind of approach is only possible in our original Kaede mouse system and by collaboration among research centers within RIKEN,” says Tomura.
Tracking the tagged cells revealed that T cells traveled from the skin to a nearby lymph node in the absence of any immune stimulus, suggesting to the researchers that immune cells migrate through non-inflamed tissues as part of their surveillance function in the body.
When the researchers painted an antigen on the skin of these mice to induce an immune response, they observed an increase in the proportion of T cells in the nearby lymph node that had come from the skin. In mice with depleted immunosuppressive Tregs, they recorded an increase in skin swelling after antigen exposure. The team therefore believes that Tregs are required to reduce inflammation within the skin.
In tissue culture experiments, Tomura, Kabashima and colleagues found that the Tregs sourced from inflamed skin suppressed the proliferation of immune cells from the lymph node, better than Tregs that had not come from skin. The researchers suggest that was probably because skin Tregs expressed higher levels of anti-inflammatory molecules.
When they injected Tregs from inflamed skin of one mouse into inflamed skin of other mice, those Tregs reduced swelling better than cells from non-inflamed skin. The researchers also observed Tregs moving to newly inflamed areas of skin from other areas.
Since Tregs can travel to and from the skin while controlling immune responses in that organ, the researchers suggest that enhancing Treg migration or function could therefore be a promising therapeutic approach to dampen inflammation in various organs.
The corresponding author for this highlight is based at the Laboratory for Autoimmune Regulation, RIKEN Research Center for Allergy and Immunology
1. Tomura, M., Honda, T., Tanizaki, H., Otsuka, A., Egawa, G., Tokura, Y. Waldmann, H., Hori, S., Cyster, J.G., Watanabe, T., Miyachi, Y., Kanagawa, O. & Kabashima, K. Activated regulatory T cells are the major T cell type emigrating from the skin during a cutaneous immune response in mice. The Journal of Clinical Investigation 120, 883–893 (2010)
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