Dermal regulatory T cells display distinct migratory behavior that is modulated during adaptive and innate inflammation

Zachary Chow, Scott Norman Mueller, James Antony Deane, Michael John Hickey

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Regulatory T cells (Tregs) are important in controlling skin inflammation, an effect dependent on their ability to home to this organ. However, little is known regarding their behavior in the skin. In this study, we used multiphoton imaging in Foxp3-GFP mice to examine the behavior of endogenous Tregs in resting and inflamed skin. Although Tregs were readily detectable in the uninflamed dermis, most were nonmotile. Induction of contact sensitivity increased the proportion of motile Tregs, and also induced Treg recruitment. This response was significantly blunted in mice challenged with an irrelevant hapten, or by inhibition of effector cell recruitment, indicating a role for T cell-dependent inflammation in induction of Treg migration. Moreover, induction of Treg migration was inhibited by local injection of a CCR4 antagonist, indicating a role for CCR4 in this response. Exposure of naive mice to hapten also induced an increase in the proportion of migratory Tregs, demonstrating that innate signals can also induce Treg migration. Simultaneous examination of the migration of CD4(+) effector cells and Tregs in the same region of uninflamed skin demonstrated that effector cells behaved differently, being uniformly highly migratory. These findings indicate that Treg behavior in skin differs from that of CD4(+) effector cells, in that only a low proportion of Tregs is migratory under resting conditions. However, in response to both adaptive and innate inflammation, the proportion of migratory Tregs increases, raising the possibility that this response is important in multiple forms of skin inflammation.
Original languageEnglish
Pages (from-to)3049 - 3056
Number of pages8
JournalJournal of Immunology
Volume191
Issue number6
DOIs
Publication statusPublished - 2013

Cite this

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title = "Dermal regulatory T cells display distinct migratory behavior that is modulated during adaptive and innate inflammation",
abstract = "Regulatory T cells (Tregs) are important in controlling skin inflammation, an effect dependent on their ability to home to this organ. However, little is known regarding their behavior in the skin. In this study, we used multiphoton imaging in Foxp3-GFP mice to examine the behavior of endogenous Tregs in resting and inflamed skin. Although Tregs were readily detectable in the uninflamed dermis, most were nonmotile. Induction of contact sensitivity increased the proportion of motile Tregs, and also induced Treg recruitment. This response was significantly blunted in mice challenged with an irrelevant hapten, or by inhibition of effector cell recruitment, indicating a role for T cell-dependent inflammation in induction of Treg migration. Moreover, induction of Treg migration was inhibited by local injection of a CCR4 antagonist, indicating a role for CCR4 in this response. Exposure of naive mice to hapten also induced an increase in the proportion of migratory Tregs, demonstrating that innate signals can also induce Treg migration. Simultaneous examination of the migration of CD4(+) effector cells and Tregs in the same region of uninflamed skin demonstrated that effector cells behaved differently, being uniformly highly migratory. These findings indicate that Treg behavior in skin differs from that of CD4(+) effector cells, in that only a low proportion of Tregs is migratory under resting conditions. However, in response to both adaptive and innate inflammation, the proportion of migratory Tregs increases, raising the possibility that this response is important in multiple forms of skin inflammation.",
author = "Zachary Chow and Mueller, {Scott Norman} and Deane, {James Antony} and Hickey, {Michael John}",
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Dermal regulatory T cells display distinct migratory behavior that is modulated during adaptive and innate inflammation. / Chow, Zachary; Mueller, Scott Norman; Deane, James Antony; Hickey, Michael John.

In: Journal of Immunology, Vol. 191, No. 6, 2013, p. 3049 - 3056.

Research output: Contribution to journalArticleResearchpeer-review

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AB - Regulatory T cells (Tregs) are important in controlling skin inflammation, an effect dependent on their ability to home to this organ. However, little is known regarding their behavior in the skin. In this study, we used multiphoton imaging in Foxp3-GFP mice to examine the behavior of endogenous Tregs in resting and inflamed skin. Although Tregs were readily detectable in the uninflamed dermis, most were nonmotile. Induction of contact sensitivity increased the proportion of motile Tregs, and also induced Treg recruitment. This response was significantly blunted in mice challenged with an irrelevant hapten, or by inhibition of effector cell recruitment, indicating a role for T cell-dependent inflammation in induction of Treg migration. Moreover, induction of Treg migration was inhibited by local injection of a CCR4 antagonist, indicating a role for CCR4 in this response. Exposure of naive mice to hapten also induced an increase in the proportion of migratory Tregs, demonstrating that innate signals can also induce Treg migration. Simultaneous examination of the migration of CD4(+) effector cells and Tregs in the same region of uninflamed skin demonstrated that effector cells behaved differently, being uniformly highly migratory. These findings indicate that Treg behavior in skin differs from that of CD4(+) effector cells, in that only a low proportion of Tregs is migratory under resting conditions. However, in response to both adaptive and innate inflammation, the proportion of migratory Tregs increases, raising the possibility that this response is important in multiple forms of skin inflammation.

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