Activated regulatory T cells are the major T cell type emigrating from the skin during a cutaneous immune response in mice
Michio Tomura ... Osami Kanagawa, Kenji Kabashima
Michio Tomura ... Osami Kanagawa, Kenji Kabashima
Published March 1, 2010
Citation Information: J Clin Invest. 2010;120(3):883-893. doi:10.1172/JCI40926.
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Categories: Research Article Dermatology

Activated regulatory T cells are the major T cell type emigrating from the skin during a cutaneous immune response in mice

Abstract

Tregs play an important role in protecting the skin from autoimmune attack. However, the extent of Treg trafficking between the skin and draining lymph nodes (DLNs) is unknown. We set out to investigate this using mice engineered to express the photoconvertible fluorescence protein Kaede, which changes from green to red when exposed to violet light. By exposing the skin of Kaede-transgenic mice to violet light, we were able to label T cells in the periphery under physiological conditions with Kaede-red and demonstrated that both memory phenotype CD4+Foxp3– non-Tregs and CD4+Foxp3+ Tregs migrated from the skin to DLNs in the steady state. During cutaneous immune responses, Tregs constituted the major emigrants and inhibited immune responses more robustly than did LN-resident Tregs. We consistently observed that cutaneous immune responses were prolonged by depletion of endogenous Tregs in vivo. In addition, the circulating Tregs specifically included activated CD25hi Tregs that demonstrated a strong inhibitory function. Together, our results suggest that Tregs in circulation infiltrate the periphery, traffic to DLNs, and then recirculate back to the skin, contributing to the downregulation of cutaneous immune responses.

Authors

Michio Tomura, Tetsuya Honda, Hideaki Tanizaki, Atsushi Otsuka, Gyohei Egawa, Yoshiki Tokura, Herman Waldmann, Shohei Hori, Jason G. Cyster, Takeshi Watanabe, Yoshiki Miyachi, Osami Kanagawa, Kenji Kabashima

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Cell migration from the skin to the DLN in the steady state. (A) Kaede-T...

Figure 1

Cell migration from the skin to the DLN in the steady state.

(A) Kaede-Tg mice were photoconverted on the clipped abdominal skin as described in Methods and observed with a fluorescence stereoscopic microscope. Nonphotoconverted clipped skin is shown as a control (middle). Note: nonclipped area remains black since light cannot reach. (B) Skin and draining axillary LN cells resected immediately after violet light exposure of the abdominal skin and resected skin cells not exposed to violet light were subjected to flow cytometric analysis to evaluate the photoconversion. (C and D) Twenty-four hours after photoconversion of the abdominal skin, cells from the draining axillary and other nondraining cervical and popliteal peripheral LNs were stained with CD11c and CD4 mAbs (C) and CD4 and CD44 mAbs (D) and subjected to flow cytometry. These data are representative of at least 5 experiments. Numbers within plots or histograms (B–D) indicate percentage of cells in the respective areas.