Integrated STAT3 and Ikaros Zinc Finger Transcription Factor Activities Regulate Bcl-6 Expression in CD4 Th Cells

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2017 Aug 30

PMID 28848064

Citations 31

Authors

Kaitlin A Read

Michael D Powell

Chandra E Baker

Bharath K Sreekumar

Veronica M Ringel-Scaia

Holly Bachus

R Emily Martin

Ian D Cooley

Irving C Allen

Andre Ballesteros-Tato

Kenneth J Oestreich

Affiliations

Soon will be listed here.

Abstract

B cell lymphoma-6 (Bcl-6) is a transcriptional repressor that is required for the differentiation of T follicular helper (T) cell populations. Currently, the molecular mechanisms underlying the transcriptional regulation of Bcl-6 expression are unclear. In this study, we have identified the Ikaros zinc finger transcription factors Aiolos and Ikaros as novel regulators of Bcl-6. We found that increased expression of Bcl-6 in CD4 Th cell populations correlated with enhanced enrichment of Aiolos and Ikaros at the promoter. Furthermore, overexpression of Aiolos or Ikaros, but not the related family member Eos, was sufficient to induce promoter activity. Intriguingly, STAT3, a known Bcl-6 transcriptional regulator, physically interacted with Aiolos to form a transcription factor complex capable of inducing the expression of and the T-associated cytokine receptor Importantly, in vivo studies revealed that the expression of Aiolos was elevated in Ag-specific T cells compared with that observed in non-T effector Th cells generated in response to influenza infection. Collectively, these data describe a novel regulatory mechanism through which STAT3 and the Ikaros zinc finger transcription factors Aiolos and Ikaros cooperate to regulate Bcl-6 expression.

Citing Articles

Aiolos promotes CXCR3 expression on Th1 cells via positive regulation of IFN-γ/STAT1 signaling.

Leonard M, Jones D, Read K, Pokhrel S, Tuazon J, Warren R JCI Insight. 2024; 10(1.

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Age-associated myeloid malignancies - the role of STAT3 and STAT5 in myelodysplastic syndrome and acute myeloid leukemia.

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RACK1 enhances STAT3 stability and promotes T follicular helper cell development and function during blood-stage Plasmodium infection in mice.

Cheng Q, Yang X, Zou T, Sun L, Zhang X, Deng L PLoS Pathog. 2024; 20(7):e1012352.

PMID: 39024388 PMC: 11288429. DOI: 10.1371/journal.ppat.1012352.

AIOLOS-Associated Inborn Errors of Immunity.

Yamashita M, Morio T J Clin Immunol. 2024; 44(6):128.

PMID: 38773004 PMC: 11108880. DOI: 10.1007/s10875-024-01730-9.

Cytotoxic Programming of CD4+ T Cells Is Regulated by Opposing Actions of the Related Transcription Factors Eos and Aiolos.

Jones D, Tuazon J, Read K, Leonard M, Pokhrel S, Sreekumar B J Immunol. 2024; 212(7):1129-1141.

PMID: 38363226 PMC: 10948294. DOI: 10.4049/jimmunol.2300748.

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