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Blood, 1 January 2007, Vol. 109, No. 1, pp. 194-202. Prepublished online as a Blood First Edition Paper on September 12, 2006; DOI 10.1182/blood-2006-02-002873. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-02-002873v1 109/1/194    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Clark, R. A. Articles by Kupper, T. S. Search for Related Content PubMed PubMed Citation Articles by Clark, R. A. Articles by Kupper, T. S. Related Collections Immunobiology Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY IL-15 and dermal fibroblasts induce proliferation of natural regulatory T cells isolated from human skin Rachael A. Clark1,, and Thomas S. Kupper1 1 Department of Dermatology, Brigham and Women's Hospital and the Harvard Skin Disease Research Center, Boston, MA Regulatory T cells (Tregs) are crucial for the induction and maintenance of self-tolerance and are present in peripheral tissues such as skin and gut under normal, noninflamed conditions. We report isolation and expansion of the Treg population resident in normal human skin. Cutaneous Tregs expressed high levels of CD25, L-selectin, GITR, FOXP3, and intracellular CTLA-4, low levels of CD69, and high levels of the skin-homing addressins CLA, CCR4, and CCR6. Skin Tregs suppressed the proliferation of CD25lo T cells from the same skin sample in response to CD3 and CD28 antibodies. Suppression was dependent on cell contact and not affected by neutralizing antibodies to interleukin-10 (IL-10) and transforming growth factor-ß (TGF-ß). Surprisingly, cutaneous Tregs proliferated in an antigen-independent manner when cultured in contact with dermal fibroblasts and IL-15, conditions similar to those found in chronically inflamed skin. We hypothesize that local proliferation of Tregs may occur within inflamed skin and could serve as a brake for cutaneous inflammation as well as a mechanism for the homeostatic proliferation of natural Tregs that has been observed within intact organisms. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Takahashi, Y. Kano, Y. Yamazaki, M. Kimishima, Y. Mizukawa, and T. Shiohara Defective Regulatory T Cells In Patients with Severe Drug Eruptions: Timing of the Dysfunction Is Associated with the Pathological Phenotype and Outcome J. Immunol., June 15, 2009; 182(12): 8071 - 8079. [Abstract] [Full Text] [PDF] I. Kotsianidis, E. Nakou, I. Bouchliou, A. Tzouvelekis, E. Spanoudakis, P. Steiropoulos, I. Sotiriou, V. Aidinis, D. Margaritis, C. Tsatalas, et al. Global Impairment of CD4+CD25+FOXP3+ Regulatory T Cells in Idiopathic Pulmonary Fibrosis Am. J. Respir. Crit. Care Med., June 15, 2009; 179(12): 1121 - 1130. [Abstract] [Full Text] [PDF] J. C. Dudda, N. Perdue, E. Bachtanian, and D. J. Campbell Foxp3+ regulatory T cells maintain immune homeostasis in the skin J. Exp. Med., July 7, 2008; 205(7): 1559 - 1565. [Abstract] [Full Text] [PDF] S. Rana, S. N. Byrne, L. J. MacDonald, C. Y.-Y. Chan, and G. M. Halliday Ultraviolet B Suppresses Immunity by Inhibiting Effector and Memory T Cells Am. J. Pathol., April 1, 2008; 172(4): 993 - 1004. [Abstract] [Full Text] [PDF] L. Passerini, S. E. Allan, M. Battaglia, S. Di Nunzio, A. N. Alstad, M. K. Levings, M. G. Roncarolo, and R. Bacchetta STAT5-signaling cytokines regulate the expression of FOXP3 in CD4+CD25+ regulatory T cells and CD4+CD25- effector T cells Int. Immunol., March 1, 2008; 20(3): 421 - 431. [Abstract] [Full Text] [PDF] Y. Kagimoto, H. Yamada, T. Ishikawa, N. Maeda, F. Goshima, Y. Nishiyama, M. Furue, and Y. Yoshikai A regulatory role of interleukin 15 in wound healing and mucosal infection in mice J. Leukoc. Biol., January 1, 2008; 83(1): 165 - 172. [Abstract] [Full Text] [PDF] M. A. Haniffa, X.-N. Wang, U. Holtick, M. Rae, J. D. Isaacs, A. M. Dickinson, C. M. U. Hilkens, and M. P. Collin Adult Human Fibroblasts Are Potent Immunoregulatory Cells and Functionally Equivalent to Mesenchymal Stem Cells J. Immunol., August 1, 2007; 179(3): 1595 - 1604. [Abstract] [Full Text] [PDF]

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