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Programming of regulatory T cells from pluripotent stem cells and prevention of autoimmunity.

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Programming of regulatory T cells from pluripotent stem cells and prevention of autoimmunity.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Haque, Rizwanul Wu, Yuzhang Zhao, Baohua Bian, Yanqing Lei, Fengyang Xiong, Xiaofang Song, Jianxun
Description	Country affiliation: United States Author Affiliation: Haque R ( Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.)
Abstract	Regulatory T (Treg) cells are being used to treat autoimmunity and prevent organ rejection; however, Treg cell-based therapies have been hampered by the technical limitation in obtaining a high number of functional Treg cells. In this study, we show how to generate functional Treg cells from induced pluripotent stem (iPS) cells and to determine the potential role of such cells for Treg cell-based immunotherapy against autoimmunity in a therapeutic setting. Ligation of a Notch ligand and transduction of the gene Foxp3 induce iPS cells to differentiate into Treg cells. Expression of Foxp3 and coculture on Notch ligand-expressing stromal cells augment expression of CD3, TCR, CD4, CD25, and CTLA-4 on iPS cell-differentiated Treg cells, which are able to secrete TGF-ß and IL-10 both in vivo and in vitro. Importantly, adoptive transfer of iPS cell-derived Treg cells expressing large amounts of Foxp3 and Bcl-x(L) significantly suppresses host immune responses and reduces arthritis development within murine models. These data suggest that Notch signaling and Foxp3 regulate the development and function of Treg cells derived from iPS cells. Our results provide a novel approach for generating potentially therapeutic Treg cells for the treatment of autoimmune diseases.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1200633
Journal	The Journal of Immunology
Issue Number	3
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-08-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Autoimmune Diseases Prevention & Control Cell Differentiation Immunology Pluripotent Stem Cells Cytology T-lymphocytes, Regulatory Animals Arthritis, Experimental Pathology Cell Line Cells, Cultured Coculture Techniques Mice Mice, 129 Strain Mice, Inbred C57bl Mice, Inbred Dba Mice, Knockout Mice, Transgenic Organ Culture Techniques Transplantation Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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Cyclin-dependent kinase 2 controls peripheral immune tolerance.

Dendritic cell-specific disruption of TGF-ß receptor II leads to altered regulatory T cell phenotype and spontaneous multiorgan autoimmunity.

Autoimmune regulator (AIRE)-deficient CD8+CD28low regulatory T lymphocytes fail to control experimental colitis.

Vasoactive intestinal peptide induces regulatory dendritic cells with therapeutic effects on autoimmune disorders.

Regulatory T cells more effectively suppress Th1-induced airway inflammation compared with Th2.

CD4+ T cells and Lactobacillus casei control relapsing colitis mediated by CD8+ T cells.

Directed differentiation of induced pluripotent stem cells towards T lymphocytes.

A novel IL-10-independent regulatory role for B cells in suppressing autoimmunity by maintenance of regulatory T cells via GITR ligand.

Regulatory T cells enhance mast cell production of IL-6 via surface-bound TGF-ß.

Programming of regulatory T cells from pluripotent stem cells and prevention of autoimmunity.

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Programming of regulatory T cells from pluripotent stem cells and prevention of autoimmunity.