FOXP3 regulates TLR10 expression in human T regulatory cells

Michael P. Bell, Phyllis A. Svingen, Meher K. Rahman, Yuning Xiong, William Alvis Faubion

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Although functionally relevant TLRs can be expressed on human T regulatory (Treg) cells, little is known about the transcriptional control of their expression. We hypothesized that the transcription factor forkhead box P3 (FOXP3) regulates the expression of TLR family members in human Treg cells. Using primary human T cells and a reporter assay in Jurkat T cell lines, we dissected the regulation of TLR10, a TLR highly expressed in human Treg cells. We determined that TLR10 was expressed in human Treg cells through quantitative PCR, Western blotting, and flow cytometry. DNA binding of FOXP3 to a suspected cis-regulatory region in proximity to the transcription start site of TLR10 was established through EMSA and chromatin immunoprecipitation. Transcriptional control of TLR10 by FOXP3 was determined through luciferase reporter assays in Jurkat T cell lines. Relevance of FOXP3 to TLR10 gene transcription in primary T cells was established through the transfection of primary CD4 +CD25 -FOXP3 - T cells with a FOXP3 expression vector, which resulted in prompt production of TLR10 mRNA. Enhanced expression of TLR10 protein in primary Treg cells was induced in a calcium-dependent fashion through TCR activation. The suspected promotional cooperation between FOXP3 and NF-AT was established in the abolition of the luciferase signal upon transfection of a mutant FOXP3 devoid of NF-AT-binding activity. These results suggest that human Treg cells express TLR10, and this expression is regulated through a cooperative complex of FOXP3 and NF-AT.

Original languageEnglish (US)
Pages (from-to)1893-1900
Number of pages8
JournalJournal of Immunology
Volume179
Issue number3
StatePublished - Aug 1 2007

Fingerprint

Regulatory T-Lymphocytes
T-Lymphocytes
Jurkat Cells
Luciferases
Transfection
Forkhead Transcription Factors
Cell Line
Chromatin Immunoprecipitation
Nucleic Acid Regulatory Sequences
Transcription Initiation Site
Flow Cytometry
Western Blotting
Calcium
Polymerase Chain Reaction
Messenger RNA
DNA
Genes
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Bell, M. P., Svingen, P. A., Rahman, M. K., Xiong, Y., & Faubion, W. A. (2007). FOXP3 regulates TLR10 expression in human T regulatory cells. Journal of Immunology, 179(3), 1893-1900.

FOXP3 regulates TLR10 expression in human T regulatory cells. / Bell, Michael P.; Svingen, Phyllis A.; Rahman, Meher K.; Xiong, Yuning; Faubion, William Alvis.

In: Journal of Immunology, Vol. 179, No. 3, 01.08.2007, p. 1893-1900.

Research output: Contribution to journalArticle

Bell, MP, Svingen, PA, Rahman, MK, Xiong, Y & Faubion, WA 2007, 'FOXP3 regulates TLR10 expression in human T regulatory cells', Journal of Immunology, vol. 179, no. 3, pp. 1893-1900.
Bell MP, Svingen PA, Rahman MK, Xiong Y, Faubion WA. FOXP3 regulates TLR10 expression in human T regulatory cells. Journal of Immunology. 2007 Aug 1;179(3):1893-1900.
Bell, Michael P. ; Svingen, Phyllis A. ; Rahman, Meher K. ; Xiong, Yuning ; Faubion, William Alvis. / FOXP3 regulates TLR10 expression in human T regulatory cells. In: Journal of Immunology. 2007 ; Vol. 179, No. 3. pp. 1893-1900.
@article{95409bc52cc44df18271640bc0d3ddb6,
title = "FOXP3 regulates TLR10 expression in human T regulatory cells",
abstract = "Although functionally relevant TLRs can be expressed on human T regulatory (Treg) cells, little is known about the transcriptional control of their expression. We hypothesized that the transcription factor forkhead box P3 (FOXP3) regulates the expression of TLR family members in human Treg cells. Using primary human T cells and a reporter assay in Jurkat T cell lines, we dissected the regulation of TLR10, a TLR highly expressed in human Treg cells. We determined that TLR10 was expressed in human Treg cells through quantitative PCR, Western blotting, and flow cytometry. DNA binding of FOXP3 to a suspected cis-regulatory region in proximity to the transcription start site of TLR10 was established through EMSA and chromatin immunoprecipitation. Transcriptional control of TLR10 by FOXP3 was determined through luciferase reporter assays in Jurkat T cell lines. Relevance of FOXP3 to TLR10 gene transcription in primary T cells was established through the transfection of primary CD4 +CD25 -FOXP3 - T cells with a FOXP3 expression vector, which resulted in prompt production of TLR10 mRNA. Enhanced expression of TLR10 protein in primary Treg cells was induced in a calcium-dependent fashion through TCR activation. The suspected promotional cooperation between FOXP3 and NF-AT was established in the abolition of the luciferase signal upon transfection of a mutant FOXP3 devoid of NF-AT-binding activity. These results suggest that human Treg cells express TLR10, and this expression is regulated through a cooperative complex of FOXP3 and NF-AT.",
author = "Bell, {Michael P.} and Svingen, {Phyllis A.} and Rahman, {Meher K.} and Yuning Xiong and Faubion, {William Alvis}",
year = "2007",
month = "8",
day = "1",
language = "English (US)",
volume = "179",
pages = "1893--1900",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - FOXP3 regulates TLR10 expression in human T regulatory cells

AU - Bell, Michael P.

AU - Svingen, Phyllis A.

AU - Rahman, Meher K.

AU - Xiong, Yuning

AU - Faubion, William Alvis

PY - 2007/8/1

Y1 - 2007/8/1

N2 - Although functionally relevant TLRs can be expressed on human T regulatory (Treg) cells, little is known about the transcriptional control of their expression. We hypothesized that the transcription factor forkhead box P3 (FOXP3) regulates the expression of TLR family members in human Treg cells. Using primary human T cells and a reporter assay in Jurkat T cell lines, we dissected the regulation of TLR10, a TLR highly expressed in human Treg cells. We determined that TLR10 was expressed in human Treg cells through quantitative PCR, Western blotting, and flow cytometry. DNA binding of FOXP3 to a suspected cis-regulatory region in proximity to the transcription start site of TLR10 was established through EMSA and chromatin immunoprecipitation. Transcriptional control of TLR10 by FOXP3 was determined through luciferase reporter assays in Jurkat T cell lines. Relevance of FOXP3 to TLR10 gene transcription in primary T cells was established through the transfection of primary CD4 +CD25 -FOXP3 - T cells with a FOXP3 expression vector, which resulted in prompt production of TLR10 mRNA. Enhanced expression of TLR10 protein in primary Treg cells was induced in a calcium-dependent fashion through TCR activation. The suspected promotional cooperation between FOXP3 and NF-AT was established in the abolition of the luciferase signal upon transfection of a mutant FOXP3 devoid of NF-AT-binding activity. These results suggest that human Treg cells express TLR10, and this expression is regulated through a cooperative complex of FOXP3 and NF-AT.

AB - Although functionally relevant TLRs can be expressed on human T regulatory (Treg) cells, little is known about the transcriptional control of their expression. We hypothesized that the transcription factor forkhead box P3 (FOXP3) regulates the expression of TLR family members in human Treg cells. Using primary human T cells and a reporter assay in Jurkat T cell lines, we dissected the regulation of TLR10, a TLR highly expressed in human Treg cells. We determined that TLR10 was expressed in human Treg cells through quantitative PCR, Western blotting, and flow cytometry. DNA binding of FOXP3 to a suspected cis-regulatory region in proximity to the transcription start site of TLR10 was established through EMSA and chromatin immunoprecipitation. Transcriptional control of TLR10 by FOXP3 was determined through luciferase reporter assays in Jurkat T cell lines. Relevance of FOXP3 to TLR10 gene transcription in primary T cells was established through the transfection of primary CD4 +CD25 -FOXP3 - T cells with a FOXP3 expression vector, which resulted in prompt production of TLR10 mRNA. Enhanced expression of TLR10 protein in primary Treg cells was induced in a calcium-dependent fashion through TCR activation. The suspected promotional cooperation between FOXP3 and NF-AT was established in the abolition of the luciferase signal upon transfection of a mutant FOXP3 devoid of NF-AT-binding activity. These results suggest that human Treg cells express TLR10, and this expression is regulated through a cooperative complex of FOXP3 and NF-AT.

UR - http://www.scopus.com/inward/record.url?scp=34548650657&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548650657&partnerID=8YFLogxK

M3 - Article

C2 - 17641056

AN - SCOPUS:34548650657

VL - 179

SP - 1893

EP - 1900

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -