Memory regulatory T cells reside in human skin
Robert Sanchez Rodriguez, … , Abul K. Abbas, Michael D. Rosenblum
Robert Sanchez Rodriguez, … , Abul K. Abbas, Michael D. Rosenblum
Published February 10, 2014
Citation Information: J Clin Invest. 2014;124(3):1027-1036. https://doi.org/10.1172/JCI72932.
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Research Article Immunology

Memory regulatory T cells reside in human skin

Abstract

Regulatory T cells (Tregs), which are characterized by expression of the transcription factor Foxp3, are a dynamic and heterogeneous population of cells that control immune responses and prevent autoimmunity. We recently identified a subset of Tregs in murine skin with properties typical of memory cells and defined this population as memory Tregs (mTregs). Due to the importance of these cells in regulating tissue inflammation in mice, we analyzed this cell population in humans and found that almost all Tregs in normal skin had an activated memory phenotype. Compared with mTregs in peripheral blood, cutaneous mTregs had unique cell surface marker expression and cytokine production. In normal human skin, mTregs preferentially localized to hair follicles and were more abundant in skin with high hair density. Sequence comparison of TCRs from conventional memory T helper cells and mTregs isolated from skin revealed little homology between the two cell populations, suggesting that they recognize different antigens. Under steady-state conditions, mTregs were nonmigratory and relatively unresponsive; however, in inflamed skin from psoriasis patients, mTregs expanded, were highly proliferative, and produced low levels of IL-17. Taken together, these results identify a subset of Tregs that stably resides in human skin and suggest that these cells are qualitatively defective in inflammatory skin disease.

Authors

Robert Sanchez Rodriguez, Mariela L. Pauli, Isaac M. Neuhaus, Siegrid S. Yu, Sarah T. Arron, Hobart W. Harris, Sara Hsin-Yi Yang, Bryan A. Anthony, Francis M. Sverdrup, Elisabeth Krow-Lucal, Tippi C. MacKenzie, David S. Johnson, Everett H. Meyer, Andrea Löhr, Andro Hsu, John Koo, Wilson Liao, Rishu Gupta, Maya G. Debbaneh, Daniel Butler, Monica Huynh, Ethan C. Levin, Argentina Leon, William Y. Hoffman, Mary H. McGrath, Michael D. Alvarado, Connor H. Ludwig, Hong-An Truong, Megan M. Maurano, Iris K. Gratz, Abul K. Abbas, Michael D. Rosenblum

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Figure 2

Tregs in human skin have an activated effector memory phenotype.

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Tregs in human skin have an activated effector memory phenotype. (A and ...
(A and B) Expression of activation markers, memory markers, and cytokines from viable CD3+CD4+CD45RO+ T cells in PBMCs and skin isolated from healthy adults. Skin used for cytokine analysis in B was harvested from face or scalp. Scatter plots in B represent the percentage of cytokine-producing cells within Foxp3+ and Foxp3– gates. All gates are based on isotype control staining or unstimulated controls (for cytokine production in B). EC, extracellular. (C) Percentage of demethylation of genomic DNA in intron 1 of the FOXP3 gene (TSDR locus) of mTregs and mTconvs in PBMCs and skin isolated from healthy adults. Each pie chart represents a sorted population purified from a different donor, and numeric values within pie charts represent the percentage of demethylation at the TSDR locus. Numeric values in parentheses below each chart represent the percentage of Foxp3-expressing cells within each purified cell population. Cell sorting strategy is shown in Supplemental Figure 4. Results in A and B are representative data from more than fifteen independent experiments. Results in C are from three or more replicate experiments. P values were determined using a 2-tailed unpaired Student’s t test.