Biomol Ther (Seoul)  
Enforced Expression of CXCR5 Drives T Follicular Regulatory-Like Features in Foxp3+ T Cells
Young Uk Kim1,†, Byung-Seok Kim2,†, Hoyong Lim2, Rick A. Wetsel1 and Yeonseok Chung1,2,*
1Center for Immunology and Autoimmune Diseases, Institute of Molecular Medicine, The University of Texas Medical School, Houston, TX 77030, USA
2Laboratory of Immune Regulation, Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea
E-mail: yeonseok@snu.ac.kr
Tel: +82-2-880-7874, Fax: +82-2-872-1795
The first two authors contributed equally to this work.
Received: April 5, 2016; Revised: May 25, 2016; Accepted: June 7, 2016; Published online: October 17, 2016.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
CXCR5+ T follicular helper (Tfh) cells are associated with aberrant autoantibody production in patients with antibody-mediated autoimmune diseases including lupus. Follicular regulatory T (Tfr) cells expressing CXCR5 and Bcl6 have been recently identified as a specialized subset of Foxp3+ regulatory T (Treg) cells that control germinal center reactions. In this study, we show that retroviral transduction of CXCR5 gene in Foxp3+ Treg cells induced a stable expression of functional CXCR5 on their surface. The Cxcr5-transduced Treg cells maintained the expression of Treg cell signature genes and the suppressive activity. The expression of CXCR5 as well as Foxp3 in the transduced Treg cells appeared to be stable in vivo in an adoptive transfer experiment. Moreover, Cxcr5-transduced Treg cells preferentially migrated toward the CXCL13 gradient, leading to an effective suppression of antibody production from B cells stimulated with Tfh cells. Therefore, our results demonstrate that enforced expression of CXCR5 onto Treg cells efficiently induces Tfr cell-like properties, which might be a promising cellular therapeutic approach for the treatment of antibody-mediated autoimmune diseases.
Keywords: CXCR5, Retroviral transduction, Treg cell, Tfh cell, Tfr cell, Germinal center reactions


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