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Enforced Expression of CXCR5 Drives T Follicular Regulatory-Like Features in Foxp3
- Source :
- Biomolecules & Therapeutics
- Publication Year :
- 2016
-
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.
- Subjects :
- 0301 basic medicine
Adoptive cell transfer
chemical and pharmacologic phenomena
Biology
Biochemistry
Tfh cell
CXCR5
03 medical and health sciences
0302 clinical medicine
Drug Discovery
medicine
Germinal center reactions
CXCL13
Gene
Pharmacology
Systemic lupus erythematosus
Tfr cell
FOXP3
Germinal center
hemic and immune systems
BCL6
medicine.disease
Treg cell
3. Good health
Cell biology
Retroviral transduction
030104 developmental biology
Immunology
Molecular Medicine
Original Article
030215 immunology
Subjects
Details
- ISSN :
- 19769148
- Volume :
- 25
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Biomoleculestherapeutics
- Accession number :
- edsair.doi.dedup.....dd9f7099208324681045695deebe6243