title: Enforced Expression of CXCR5 Drives T Follicular Regulatory-Like Features in Foxp3+T Cells.
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 ofCXCR5gene in Foxp3+Treg cells induced a stable expression of functional CXCR5 on their surface. TheCxcr5-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 stablein vivoin 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.
authors.affiliation: Center for Immunology and Autoimmune Diseases, Institute of Molecular Medicine, The University of Texas Medical School, Houston, TX 77030, USA.
authors.forename: Young Uk
authors.initials: YU
authors.lastname: Kim
authors.affiliation: Laboratory of Immune Regulation, Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Byung-Seok
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Laboratory of Immune Regulation, Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Hoyong
authors.initials: H
authors.lastname: Lim
authors.affiliation: Center for Immunology and Autoimmune Diseases, Institute of Molecular Medicine, The University of Texas Medical School, Houston, TX 77030, USA.
authors.forename: Rick A
authors.initials: RA
authors.lastname: Wetsel
authors.affiliation: Center for Immunology and Autoimmune Diseases, Institute of Molecular Medicine, The University of Texas Medical School, Houston, TX 77030, USA.|Laboratory of Immune Regulation, Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Yeonseok
authors.initials: Y
authors.lastname: Chung
keywords: CXCR5; Germinal center reactions; Retroviral transduction; Tfh cell; Tfr cell; Treg cell