Foxp3 expression in induced T regulatory cells derived from human umbilical cord blood vs. adult peripheral blood



Foxp3 is essential for T regulatory cell (Treg) function. Broad complex-Tramtrack-Bric-a-brac domain (BTB) and Cap‘n’collar (CNC) homology 1, transcription factor 2 (BACH2) stabilizes Treg immune homeostasis in murine studies. However, little is known regarding what role, if any, BACH2 may have in Foxp3 regulation in human-induced Treg (iTreg). We examined Foxp3 expression and regulation comparing iTreg differentiated from umbilical cord blood (UCB) vs. adult blood (AB) naive CD4+ T-cells. Foxp3 expression was higher in UCB vs. AB-derived iTreg, and was sustained during 21-day expansion in vitro. The number of Foxp3+ iTreg generated from UCB vs. AB naive CD4+ T-cells was higher in iTreg differentiation conditions. In addition, UCB iTreg were more potent in suppressing T-cell proliferation compared to AB iTreg. Naive UCB CD4+ T-cells highly expressed BACH2 protein compared to AB. Putative transcriptional BACH2 binding sites were identified at the Foxp3 promoter, using BACH2 consensus sequence. Cross-linking chromatin immunoprecipitation (ChIP) showed that BACH2 binds to the Foxp3 proximal promoter in UCB iTreg, but not AB iTreg. BACH2 was transcriptionally active, as shRNA-mediated BACH2 knockdown resulted in reduction of Foxp3 gene transcription in UCB CD4+ T-cells. In summary, BACH2 serves to stabilize robust Foxp3 expression in UCB CD4+ T-cell-derived iTreg.

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We thank Daniel Zwick for editorial assistance and Dr. Bruce Torbett for valuable suggestions. This work was supported by the Abraham J. & Phyllis Katz Foundation, Atlanta, GA.

Author contributions

J-sD, FZ, and MJL conducted experiments, literature search, developed study design, analyzed data, and wrote the manuscript. AYH, WJvHF, and MF contributed to the study design, data review and interpretation, as well as writing and approval of the manuscript.

Author information


  1. Cleveland Cord Blood Center, Cleveland, OH, USA

    • Jeong-su Do
    • , Fei Zhong
    • , Wouter J. Van’t Hof
    • , Marcie Finney
    •  & Mary J. Laughlin
  2. Case Western Reserve University, Cleveland, OH, USA

    • Jeong-su Do
    • , Alex Y. Huang
    •  & Mary J. Laughlin


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The authors declare that they have no conflict of interest.

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Correspondence to Jeong-su Do.

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