Layilin Anchors Regulatory T Cells in Skin.

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  • Additional Information
    • Source:
      Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE
    • Publication Information:
      Publication: Bethesda, MD : American Association of Immunologists
      Original Publication: Baltimore : Williams & Wilkins, c1950-
    • Subject Terms:
      Carrier Proteins/*metabolism ; Membrane Glycoproteins/*metabolism ; Receptors, Lymphocyte Homing/*metabolism ; Skin/*immunology ; T-Lymphocytes, Regulatory/*immunology; 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
    • 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.)
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    • Grant Information:
      P30 DK063720 United States DK NIDDK NIH HHS; T32 AI007334 United States AI NIAID NIH HHS; R01 AR071944 United States AR NIAMS NIH HHS; S10 OD018040 United States OD NIH HHS; DP2 AR068130 United States AR NIAMS NIH HHS; R21 AR072195 United States AR NIAMS NIH HHS; R01 AR077553 United States AR NIAMS NIH HHS
    • Accession Number:
      0 (Carrier Proteins)
      0 (Membrane Glycoproteins)
      0 (Receptors, Lymphocyte Homing)
      0 (Transforming Growth Factor beta)
      0 (layilin protein, mouse)
    • Publication Date:
      Date Created: 20210902 Date Completed: 20211027 Latest Revision: 20221003
    • Publication Date:
      20240829
    • Accession Number:
      PMC8489406
    • Accession Number:
      10.4049/jimmunol.2000970
    • Accession Number:
      34470859