Identification of IL-17-producing FOXP3+ regulatory T cells in humans (89.1)

Abstract

Identification of IL-17-producing FOXP3
regulatory T cells in humans Kui Shin Vooa, Yui-Hsi Wanga, Fabio R. Santorib, Cesar Boggianob, Yi-Hong Wanga, Kazuhiko Arimaa, Laura Bovera, Shino Hanabuchia, Jahan Khalilic, Ekaterina Marinovad, Biao Zhengd, Dan R. Littmanb,1, and Yong-Jun Liua,1 Departments of aImmunology and cStem Cell Transplantation and Cellular Therapy, Center for Cancer Immunology Research, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030; bThe Howard Hughes Medical Institute, The Kimmel Center for Biology and Medicine of The Skirball Institute, New York University School of Medicine, New York, NY 10016; and dDepartment of Immunology, Baylor College of Medicine, Houston, TX 77303 Contributed by Dan R. Littman, January 15, 2009 (sent for review April 9, 2008) IL-17–producing CD4
T helper (Th17) cells have recently been defined as a unique subset of proinflammatory helper cells whose development depends on signaling initiated by IL-6 and TGF-, autocrine activity of IL-21, activation of STAT3, and induction of the orphan nuclear receptor RORt. The maintenance, expansion, and further differentiation of the committed Th17 cells depend on IL-1 and IL-23. IL-17 was originally found produced by circulating human CD45RO
memory T cells. A recent study found that human Th17 memory cells selectively express high levels of CCR6. In this study, we report that human peripheral blood and lymphoid tissue contain a significant number of CD4
FOXP3
T cells that express CCR6 and have the capacity to produce IL-17 upon activation. These cells coexpress FOXP3 and RORt transcription factors. The CD4
FOXP3
CCR6
IL-17–producing cells strongly inhibit the pro- liferation of CD4
responder T cells. CD4
CD25high-derived T-cell clones express FOXP3, RORt, and IL-17 and maintain their sup- pressive function via a cell-cell contact mechanism. We further show that human CD4
FOXP3
CCR6 regulatory T (Treg) cells differentiate into IL-17 producer cells upon

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