Faculty Opinions recommendation of Immune homeostasis enforced by co-localized effector and regulatory T cells.

Author(s):  
Michael Farrar
Immunology ◽  
2016 ◽  
Vol 148 (3) ◽  
pp. 276-286 ◽  
Author(s):  
David J. Huss ◽  
Alex F. Pellerin ◽  
Brian P. Collette ◽  
Arun K. Kannan ◽  
Liaomin Peng ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Lauren Van Zeebroeck ◽  
Rebeca Arroyo Hornero ◽  
Beatriz F. Côrte-Real ◽  
Ibrahim Hamad ◽  
Torsten B. Meissner ◽  
...  

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 α-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.


Immunity ◽  
2012 ◽  
Vol 36 (5) ◽  
pp. 873-884 ◽  
Author(s):  
Julien Seneschal ◽  
Rachael A. Clark ◽  
Ahmed Gehad ◽  
Clare M. Baecher-Allan ◽  
Thomas S. Kupper

2016 ◽  
Vol 7 (4) ◽  
pp. 313-321 ◽  
Author(s):  
Arthur Liesz ◽  
Christoph Kleinschnitz

2020 ◽  
Author(s):  
Rucha Sawlekar ◽  
Stefano Magni ◽  
Christophe Capelle ◽  
Alexandre Baron ◽  
Ni Zeng ◽  
...  

AbstractRegulatory T cells (Tregs), characterized as a CD4+CD25+FOXP3+ subset of T cells, are vital to the induction of immune tolerance and the maintenance of immune homeostasis. While target genes of Treg master regulator FOXP3 have been identified, the upstream regulatory machinery of FOXP3 still remains largely unknown. Here we dynamically model causal relationships among genes from available time-series genome-scale datasets, to predict direct or indirect regulatory genes of FOXP3 in human primary Tregs. From the whole genome, we selected five top ranked candidates for further experimental validation. Following knockdown, three out of the five candidates indeed showed significant effects on the mRNA expression of FOXP3. Further experiments showed that one out of these three predicted candidates, namely nuclear receptor binding factor 2 (NRBF2), also affected FOXP3 protein expression. These results open new doors to identify potential new mechanisms of immune related diseases.


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