| Autor: |
Zineb Mounir, Mark R. Lackner, Jennifer M. Giltnane, Vicki Plaks, Shih-Min A. Huang, Steven Magnuson, F. Anthony Romero, Andrew Glibicky, Thomas Holcomb, Somayeh S. Tarighat, Matthew P. Stokes, Wendell Jones, Katherine E. Hutchinson, Bonnie Liu, Jeffrey Eastham-Anderson, Melissa Gonzalez Edick, Sangeeta Jayakar, Marie-Claire Wagle, Ron McCord, Shrividhya Srinivasan, Christopher Lowe, Esther Wu, Joseph Castillo |
| Rok vydání: |
2023 |
| Popis: |
Regulatory T cells (Treg) are immunosuppressive and negatively impact response to cancer immunotherapies. CREB-binding protein (CBP) and p300 are closely related acetyltransferases and transcriptional coactivators. Here, we evaluate the mechanisms by which CBP/p300 regulate Treg differentiation and the consequences of CBP/p300 loss-of-function mutations in follicular lymphoma. Transcriptional and epigenetic profiling identified a cascade of transcription factors essential for Treg differentiation. Mass spectrometry analysis showed that CBP/p300 acetylates prostacyclin synthase, which regulates Treg differentiation by altering proinflammatory cytokine secretion by T and B cells. Reduced Treg presence in tissues harboring CBP/p300 loss-of-function mutations was observed in follicular lymphoma. Our findings provide novel insights into the regulation of Treg differentiation by CBP/p300, with potential clinical implications on alteration of the immune landscape.Significance:This study provides insights into the dynamic role of CBP/p300 in the differentiation of Tregs, with potential clinical implications in the alteration of the immune landscape in follicular lymphoma. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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