Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/34841
Title: Fast and Efficient Genome Editing of Human FOXP3+ Regulatory T Cells
Authors: VAN ZEEBROECK, Lauren 
ARROYO HORNERO, Rebeca 
FERNANDES CORTE-REAL, Beatriz 
HAMAD, Ibrahim 
Meissner, Torsten B.
KLEINEWIETFELD, Markus 
Issue Date: 2021
Publisher: FRONTIERS MEDIA SA
Source: FRONTIERS IN IMMUNOLOGY, 12 (Art N° 655122)
Abstract: FOXP3(+) regulatory T cells (Tregs) are central for maintaining peripheral tolerance and immune homeostasis. Because of their immunosuppressive characteristics, Tregs are a potential therapeutic target in various diseases such as autoimmunity, transplantation and infectious diseases like COVID-19. Numerous studies are currently exploring the potential of adoptive Treg therapy in different disease settings and novel genome editing techniques like CRISPR/Cas will likely widen possibilities to strengthen its efficacy. However, robust and expeditious protocols for genome editing of human Tregs are limited. Here, we describe a rapid and effective protocol for reaching high genome editing efficiencies in human Tregs without compromising cell integrity, suitable for potential therapeutic applications. By deletion of IL2RA encoding for IL-2 receptor alpha-chain (CD25) in Tregs, we demonstrated the applicability of the method for downstream functional assays and highlighted the importance for CD25 for in vitro suppressive function of human Tregs. Moreover, deletion of IL6RA (CD126) in human Tregs elicits cytokine unresponsiveness and thus may prevent IL-6-mediated instability of Tregs, making it an attractive target to potentially boost functionality in settings of adoptive Treg therapies to contain overreaching inflammation or autoimmunity. Thus, our rapid and efficient protocol for genome editing in human Tregs may advance possibilities for Treg-based cellular therapies.
Notes: Kleinewietfeld, M (corresponding author), Hasselt Univ, Vlaams Inst Biotechnol VIB, Lab Translat Immunomod, Ctr Inflammat Res IRC, Diepenbeek, Belgium.; Kleinewietfeld, M (corresponding author), Hasselt Univ, Biomed Res Inst, Dept Immunol, Diepenbeek, Belgium.
markus.kleinewielfeld@uhassell.vib.be
Keywords: regulatory T cell; CD4; IL6R; CRISPR; human; genome editing; COVID-19;;autoimmunity
Document URI: http://hdl.handle.net/1942/34841
ISSN: 1664-3224
e-ISSN: 1664-3224
DOI: 10.3389/fimmu.2021.655122
ISI #: WOS:000691310000001
Category: A1
Type: Journal Contribution
Validations: ecoom 2022
Appears in Collections:Research publications

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