Enforced Expression of CXCR5 Drives T Follicular Regulatory-Like Features in Foxp3⁺ T Cells.
10.4062/biomolther.2016.075
- Author:
Young Uk KIM
1
;
Byung Seok KIM
;
Hoyong LIM
;
Rick A WETSEL
;
Yeonseok CHUNG
Author Information
1. Center for Immunology and Autoimmune Diseases, Institute of Molecular Medicine, The University of Texas Medical School, Houston, TX 77030, USA, Republic of Korea. yeonseok@snu.ac.kr
- Publication Type:Original Article
- Keywords:
CXCR5;
Retroviral transduction;
Treg cell;
Tfh cell;
Tfr cell;
Germinal center reactions
- MeSH:
Adoptive Transfer;
Antibody Formation;
Autoimmune Diseases;
B-Lymphocytes;
Germinal Center;
Humans;
T-Lymphocytes*;
T-Lymphocytes, Regulatory;
Zidovudine
- From:Biomolecules & Therapeutics
2017;25(2):130-139
- CountryRepublic of Korea
- Language:English
-
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.
