1. Layilin Anchors Regulatory T Cells in Skin.
- Author
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Mehta P, Gouirand V, Boda DP, Zhang J, Gearty SV, Zirak B, Lowe MM, Clancy S, Boothby I, Mahuron KM, Fries A, Krummel MF, Mankoo P, Chang HW, Liu J, Moreau JM, Scharschmidt TC, Daud A, Kim E, Neuhaus IM, Harris HW, Liao W, and Rosenblum MD
- Subjects
- Animals, Carrier Proteins genetics, Cell Movement, Cells, Cultured, Humans, Immune Tolerance, Lymphocyte Activation, Membrane Glycoproteins genetics, Mice, Mice, Inbred C57BL, Mice, Knockout, Models, Immunological, Organ Specificity, Receptors, Lymphocyte Homing genetics, Transforming Growth Factor beta metabolism, Carrier Proteins metabolism, Membrane Glycoproteins metabolism, Receptors, Lymphocyte Homing metabolism, Skin immunology, T-Lymphocytes, Regulatory immunology
- Abstract
Regulatory T cells (Tregs) reside in nonlymphoid tissues where they carry out unique functions. The molecular mechanisms responsible for Treg accumulation and maintenance in these tissues are relatively unknown. Using an unbiased discovery approach, we identified LAYN (layilin), a C-type lectin-like receptor, to be preferentially and highly expressed on a subset of activated Tregs in healthy and diseased human skin. Expression of layilin on Tregs was induced by TCR-mediated activation in the presence of IL-2 or TGF-β. Mice with a conditional deletion of layilin in Tregs had reduced accumulation of these cells in tumors. However, these animals somewhat paradoxically had enhanced immune regulation in the tumor microenvironment, resulting in increased tumor growth. Mechanistically, layilin expression on Tregs had a minimal effect on their activation and suppressive capacity in vitro. However, expression of this molecule resulted in a cumulative anchoring effect on Treg dynamic motility in vivo. Taken together, our results suggest a model whereby layilin facilitates Treg adhesion in skin and, in doing so, limits their suppressive capacity. These findings uncover a unique mechanism whereby reduced Treg motility acts to limit immune regulation in nonlymphoid organs and may help guide strategies to exploit this phenomenon for therapeutic benefit., (Copyright © 2021 by The American Association of Immunologists, Inc.)
- Published
- 2021
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