HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, G.-Y. Articles by Liu, Y. Search for Related Content PubMed PubMed Citation Articles by Chen, G.-Y. Articles by Liu, Y.

Cutting Edge: Broad Expression of the FoxP3 Locus in Epithelial Cells: A Caution against Early Interpretation of Fatal Inflammatory Diseases following In Vivo Depletion of FoxP3-Expressing Cells¹

Guo-Yun Chen^*, Chong Chen^*, Lizhong Wang^*, Xing Chang^*, Pan Zheng^2,*,,, and Yang Liu^2,*,,

^* Division of Immunotherapy, Section of General Surgery, Department of Surgery, Department of Pathology, Comprehensive Cancer Center, and Program of Molecular Mechanisms of Disease, University of Michigan, Ann Arbor, MI 48109

Dogma that the regulatory T cell (Treg) prevents catastrophic autoimmunity throughout the lifespan relies on the assumption that the FoxP3 locus is transcribed exclusively in Treg. To test the assumption, we used the Rag2^–/– and the Rag2^–/– mice with the Scurfy (sf) mutation (FoxP3^sf/Y or FoxP3^sf/sf) to evaluate FoxP3 expression outside of the lymphoid system. Immunohistochemistry and real-time PCR revealed FoxP3 expression in breast epithelial cells, lung respiratory epithelial cells, and prostate epithelial cells, although not in liver, heart, and intestine. The specificity of the assays was confirmed, as the signals were ablated by the Scurfy mutation of the FoxP3 gene. Using mice with a green fluorescence protein open reading frame knocked into the 3' untranslated region of the FoxP3 locus, we showed that the locus is transcribed broadly in epithelial cells of multiple organs. These results refute an essential underlying assumption of the dogma and question the specificity of FoxP3-based Treg depletion.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This study was supported by grants from the U.S. Department of Defense and the National Institutes of Health.

² Address correspondence and reprint requests to Dr. Yang Liu and Dr. Pan Zheng, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109. E-mail addresses: yangl{at}umich.edu and panz{at}umich.edu

³ Abbreviations used in this paper: Treg, regulatory T cell; DT, diphtheria toxin; DTR, DT receptor; EGFP, enhanced GFP; Hprt, hypoxanthine phosphoribosyltransferase; sf, Scurfy; WT, wild type.

This article has been cited by other articles:

				X. Chang, P. Zheng, and Y. Liu Homeostatic Proliferation in the Mice with Germline FoxP3 Mutation and its Contribution to Fatal Autoimmunity J. Immunol., August 15, 2008; 181(4): 2399 - 2406. [Abstract] [Full Text] [PDF]