Article
Foxp3-specific deletion of CREB enhances IL-10 production and suppressive capacity of regulatory T cells
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Published: | September 4, 2017 |
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Background: CREB is a transcription factor, which is known to be required for generation and maintenance of regulatory T cells by binding and activating the TSDR in the FoxP3 locus. We investigated the role of CREB in Tregs using a Foxp3CRE with specific deletion of CREB in mice.
Methods: A Foxp3CRE specific deletion of CREB was invstigated in mice. Functional analysis of Foxp3CRE/CREBfl/fl mice was performed using flow cytometry, affymetrix array analysis, suppression assays and transfer colitis. In vitro assays of CREB phosphorylation in human PBMCs were performed.
Results: Deletion of CREB in Foxp3+ cells unexpectedly results in enhanced percentages of Tregs, which -in spite of reduced Foxp3 per cell -are highly suppressive in vitro. Furthermore CREB defiecient Tregs are characterized by enhanced expression of IL-10, ST2 and IL-13 and ameliorate intestinal inflammation in experimental colitis. Interestingly, incubation with sera from patients with autoimmune diseases, such as systemic lupus erythematosus and juvenile idiopathic arthritis inhibited CREB phosphorylation in T cells.
Conclusion: In conclusion our data suggest unexpected roles of CREB, which might be of translational relevance in autoimmune conditions.