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 6

Functional analysis of cutaneous mTregs in patients with psoriasis.

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Functional analysis of cutaneous mTregs in patients with psoriasis. (A) ...
(A) Percentage and absolute number of T cells and Tregs in nonlesional psoriatic (NL-PSO) and lesional psoriatic (L-PSO) skin from patients (middle and right panels gated on CD4+ and CD3+ cells, respectively). (B) Percentage of mTregs and mTconvs in L-PSO skin or normal healthy adult skin (Control), pregated on viable CD3+ cells. (C) Intracellular IL-17 production from mTregs and mTconvs in NL-PSO and L-PSO skin, gated on viable CD3+CD4+CD45RO+ cells. Middle panel is a representative flow cytometric plot of IL-17 production, and the scatter plot shows percentages of IL-17–producing cells within the Foxp3 gate. (D) Expression of Ki67 in mTregs and mTconvs in L-PSO skin or site-matched control skin, gated on viable CD3+CD4+CD45RO+ cells. (E) Expression of Ki67 in mTregs and mTconvs in L-PSO or control skin, gated on viable CD3+CD4+CD45RO+ cells. Lines represent paired data from a single patient. Mean deltas between Foxp3– and Foxp3+ cells when comparing PSO versus control skin are 8.340 ± 5.05 versus 0.735 ± 0.50, respectively (P = 0.132). (F) MFI of Foxp3 and CD25 expression on Ki67+ and Ki67– mTregs in L-PSO skin, gated on viable CD3+CD4+CD45RO+Foxp3+ cells. (G) Foxp3 and CD127 expression on mTregs and mTconvs in L-PSO or site-matched control skin, gated on viable CD3+CD4+CD45RO+cells. Results are combined data from five or more replicate experiments.