The transcriptional repressor Bcl6 controls the stability of regulatory T cells by intrinsic and extrinsic pathways
dc.contributor.author | Sawant, Deepali V. | |
dc.contributor.author | Wu, Hao | |
dc.contributor.author | Yao, Weiguo | |
dc.contributor.author | Sehra, Sarita | |
dc.contributor.author | Kaplan, Mark H. | |
dc.contributor.author | Dent, Alexander L. | |
dc.contributor.department | Department of Microbiology & Immunology, IU School of Medicine | en_US |
dc.date.accessioned | 2017-07-13T18:25:51Z | |
dc.date.available | 2017-07-13T18:25:51Z | |
dc.date.issued | 2015-05 | |
dc.description.abstract | Foxp3(+) regulatory T (Treg) cells are essential to maintain immune homeostasis, yet controversy exists about the stability of this cell population. Bcl6-deficient (Bcl6(-/-) ) mice develop severe and spontaneous T helper type 2 (Th2) inflammation and Bcl6-deficient Treg cells are ineffective at controlling Th2 responses. We used a lineage tracing approach to analyse the fate of Treg cells in these mice. In the periphery of Bcl6(-/-) mice, increased numbers of Foxp3-negative 'exTreg' cells were found, particularly in the CD25(+) population. ExTreg cells from Bcl6(-/-) mice expressed increased interleukin-17 (IL-17) and extremely elevated levels of Th2 cytokines compared with wild-type exTreg cells. Although Treg cells normally express only low levels of cytokines, Treg cells from Bcl6(-/-) mice secreted higher levels of IL-4, IL-5, IL-13 and IL-17 than wild-type conventional T cells. Next, Treg-specific conditional Bcl6-deficient (Bcl6(Foxp3-/-) ) mice were analysed. Bcl6(Foxp3-/-) mice do not develop inflammatory disease, indicating a requirement for non-Treg cells for inflammation in Bcl6(-/-) mice, and have normal numbers of exTreg cells. We induced Th2-type allergic airway inflammation in Bcl6(Foxp3-/-) mice, and found that while exTreg cytokine expression was normal, Bcl6-deficient Treg cells expressed higher levels of the Th2-specific regulator Gata3 than Bcl6(+) Treg cells. Bcl6(Foxp3-/-) mice had increased numbers of Th2 cells after induction of airway inflammation and increased T cells in the bronchoalveolar lavage fluid. These data show both Treg-intrinsic and Treg-extrinsic roles for Bcl6 in controlling Treg cell stability and Th2 inflammation, and support the idea that Bcl6 expression in Treg cells is critical for controlling Th2 responses. | en_US |
dc.identifier.citation | Sawant, D. V., Wu, H., Yao, W., Sehra, S., Kaplan, M. H., & Dent, A. L. (2015). The transcriptional repressor Bcl6 controls the stability of regulatory T cells by intrinsic and extrinsic pathways. Immunology, 145(1), 11–23. http://doi.org/10.1111/imm.12393 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/13442 | |
dc.language.iso | en_US | en_US |
dc.publisher | Wiley | en_US |
dc.relation.isversionof | 10.1111/imm.12393 | en_US |
dc.relation.journal | Immunology | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | Bcl6 | en_US |
dc.subject | Ex-regulatory T cells | en_US |
dc.subject | FoxP3 | en_US |
dc.subject | Regulatory T cells | en_US |
dc.subject | T helper type 2 differentiation | en_US |
dc.title | The transcriptional repressor Bcl6 controls the stability of regulatory T cells by intrinsic and extrinsic pathways | en_US |
dc.type | Article | en_US |
ul.alternative.fulltext | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405320/ | en_US |