Bcl11b prevents catastrophic autoimmunity by controlling multiple aspects of a regulatory T cell gene expression program

Syed Nurul Hasan, Amit Sharma, Sayantani Ghosh, Sung Wook Hong, Sinchita Roy-Chowdhuri, Sin Hyeog Im, Keunsoo Kang, Dipayan Rudra

Research output: Contribution to journalArticlepeer-review


Foxp3 and its protein partners establish a regulatory T (Treg) cell transcription profile and promote immunological tolerance. However, molecular features contributing to a Treg-specific gene expression program are still incompletely understood. We find that the transcription factor Bcl11b is a prominent Foxp3 cofactor with multifaceted functions in Treg biology. Optimal genomic recruitment of Foxp3 and Bcl11b is critically interdependent. Genome-wide occupancy studies coupled with gene expression profiling reveal that Bcl11b, in association with Foxp3, is primarily responsible in establishing a Treg-specific gene activation program. Furthermore, Bcl11b restricts misdirected recruitment of Foxp3 to sites, which would otherwise result in an altered Treg transcriptome profile. Consequently, Treg-specific ablation of Bcl11b results in marked breakdown of immune tolerance, leading to aggressive systemic autoimmunity. Our study provides previously underappreciated mechanistic insights into molecular events contributing to basic aspects of Treg function. Furthermore, it establishes a therapeutic target with potential implications in autoimmunity and cancer.

Original languageEnglish
Article numbereaaw0706
JournalScience Advances
Issue number8
Publication statusPublished - 2019 Aug 7

Bibliographical note

Funding Information:
We thank N. Mullapudi, Scientific Officer, Hong Kong University of Science and Technology, for technical suggestions in ChIP-seq. We also thank H. Jung for technical assistance in cell sorting. Funding: This work was supported by Project IBS-R005 from the Institute for Basic Science, Korean Ministry of Science and ICT.

Publisher Copyright:
Copyright © 2019 The Authors, some rights reserved;

All Science Journal Classification (ASJC) codes

  • General


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