Memory regulatory T cells reside in human skin

• Published in: The Journal of clinical investigation Vol. 124; no. 3; pp. 1027 - 1036
• Main Authors: Sanchez Rodriguez, Robert, Pauli, Mariela L., Neuhaus, Isaac M., Yu, Siegrid S., Arron, Sarah T., Harris, Hobart W., Yang, Sara Hsin-Yi, Anthony, Bryan A., Sverdrup, Francis M., Krow-Lucal, Elisabeth, MacKenzie, Tippi C., Johnson, David S., Meyer, Everett H., Löhr, Andrea, Hsu, Andro, Koo, John, Liao, Wilson, Gupta, Rishu, Debbaneh, Maya G., Butler, Daniel, Huynh, Monica, Levin, Ethan C., Leon, Argentina, Hoffman, William Y., McGrath, Mary H., Alvarado, Michael D., Ludwig, Connor H., Truong, Hong-An, Maurano, Megan M., Gratz, Iris K., Abbas, Abul K., Rosenblum, Michael D.
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.03.2014
• Subjects: Adult; Aged; Animals; Antigens, CD - metabolism; Biomedical research; Cell Movement; Cell Proliferation; Cells, Cultured; Cloning; Female; Flow cytometry; Forkhead Transcription Factors - metabolism; Genotype & phenotype; Hair Follicle - immunology; Hair Follicle - pathology; Humans; Identification and classification; Immune system; Immunologic Memory; Interleukin-17 - metabolism; Lymphocytes; Male; Mice; Mice, Inbred NOD; Middle Aged; Monte Carlo simulation; Phenotype; Physiological aspects; Physiological research; Population; Psoriasis - immunology; Psoriasis - pathology; Receptors, Antigen, T-Cell - metabolism; Receptors, CCR7 - metabolism; Rodents; Skin; Skin - immunology; Studies; T cell receptors; T cells; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Young Adult
• ISSN: 0021-9738; 1558-8238; 1558-8238
• DOI: 10.1172/JCI72932

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.