Cholera toxin directly enhances IL-17A production from human CD4 + T cells

Hsing Chuan Tsai, Reen Wu

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The significance of Th17 cells and IL-17A signaling in host defense and disease development has been demonstrated in various infection and autoimmune models. Additionally, the generation of Th17 cells is highly influenced by microbes. However, the specific bacterial components capable of shaping Th17 responses have not been well defined. The goals of this study were to understand how a bacterial toxin, cholera toxin (CT), modulates Th17-dominated response in isolated human CD4+ T cells, and what are the mechanisms associated with this modulation. CD4+ cells isolated from human peripheral blood were treated with CT. The levels of cytokine production and specific Th cell responses were determined by ELISA, Luminex assay, and flow cytometry. Along with the decreased production of other proinflammatory cytokines (IFN-γ , TNF-α, and IL-2), we found that CT could directly enhance the IL-17A production through a cAMP-dependent pathway. This enhancement is specific for IL-17A but not for IL-17F, IL-22, and CCL20. Interestingly, CT could increase IL-17A production only from Th17-committed cells, such as CCR6+ CD4+ T cells and in vitro-differentiated Th17 cells. Furthermore, we also demonstrated that this direct effect occurs at a transcriptional level because CT stimulates the reporter activity in Jurkat and primary CD4 + T cells transfected with the IL-17A promoter-reporter construct. This study shows that CT has the capacity to directly shape Th17 responses in the absence of APCs. Our findings highlight the potentials of bacterial toxins in the regulation of human Th17 responses.

Original languageEnglish (US)
Pages (from-to)4095-4102
Number of pages8
JournalJournal of Immunology
Volume191
Issue number8
DOIs
StatePublished - Oct 15 2013

Fingerprint

Interleukin-17
Cholera Toxin
Th17 Cells
T-Lymphocytes
Bacterial Toxins
Cytokines
Interleukin-2
human IL17A protein
Flow Cytometry
Enzyme-Linked Immunosorbent Assay
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Cholera toxin directly enhances IL-17A production from human CD4 + T cells. / Tsai, Hsing Chuan; Wu, Reen.

In: Journal of Immunology, Vol. 191, No. 8, 15.10.2013, p. 4095-4102.

Research output: Contribution to journalArticle

@article{fa3f91ff905f46a7a318aed77e3d8aad,
title = "Cholera toxin directly enhances IL-17A production from human CD4 + T cells",
abstract = "The significance of Th17 cells and IL-17A signaling in host defense and disease development has been demonstrated in various infection and autoimmune models. Additionally, the generation of Th17 cells is highly influenced by microbes. However, the specific bacterial components capable of shaping Th17 responses have not been well defined. The goals of this study were to understand how a bacterial toxin, cholera toxin (CT), modulates Th17-dominated response in isolated human CD4+ T cells, and what are the mechanisms associated with this modulation. CD4+ cells isolated from human peripheral blood were treated with CT. The levels of cytokine production and specific Th cell responses were determined by ELISA, Luminex assay, and flow cytometry. Along with the decreased production of other proinflammatory cytokines (IFN-γ , TNF-α, and IL-2), we found that CT could directly enhance the IL-17A production through a cAMP-dependent pathway. This enhancement is specific for IL-17A but not for IL-17F, IL-22, and CCL20. Interestingly, CT could increase IL-17A production only from Th17-committed cells, such as CCR6+ CD4+ T cells and in vitro-differentiated Th17 cells. Furthermore, we also demonstrated that this direct effect occurs at a transcriptional level because CT stimulates the reporter activity in Jurkat and primary CD4 + T cells transfected with the IL-17A promoter-reporter construct. This study shows that CT has the capacity to directly shape Th17 responses in the absence of APCs. Our findings highlight the potentials of bacterial toxins in the regulation of human Th17 responses.",
author = "Tsai, {Hsing Chuan} and Reen Wu",
year = "2013",
month = "10",
day = "15",
doi = "10.4049/jimmunol.1301079",
language = "English (US)",
volume = "191",
pages = "4095--4102",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "8",

}

TY - JOUR

T1 - Cholera toxin directly enhances IL-17A production from human CD4 + T cells

AU - Tsai, Hsing Chuan

AU - Wu, Reen

PY - 2013/10/15

Y1 - 2013/10/15

N2 - The significance of Th17 cells and IL-17A signaling in host defense and disease development has been demonstrated in various infection and autoimmune models. Additionally, the generation of Th17 cells is highly influenced by microbes. However, the specific bacterial components capable of shaping Th17 responses have not been well defined. The goals of this study were to understand how a bacterial toxin, cholera toxin (CT), modulates Th17-dominated response in isolated human CD4+ T cells, and what are the mechanisms associated with this modulation. CD4+ cells isolated from human peripheral blood were treated with CT. The levels of cytokine production and specific Th cell responses were determined by ELISA, Luminex assay, and flow cytometry. Along with the decreased production of other proinflammatory cytokines (IFN-γ , TNF-α, and IL-2), we found that CT could directly enhance the IL-17A production through a cAMP-dependent pathway. This enhancement is specific for IL-17A but not for IL-17F, IL-22, and CCL20. Interestingly, CT could increase IL-17A production only from Th17-committed cells, such as CCR6+ CD4+ T cells and in vitro-differentiated Th17 cells. Furthermore, we also demonstrated that this direct effect occurs at a transcriptional level because CT stimulates the reporter activity in Jurkat and primary CD4 + T cells transfected with the IL-17A promoter-reporter construct. This study shows that CT has the capacity to directly shape Th17 responses in the absence of APCs. Our findings highlight the potentials of bacterial toxins in the regulation of human Th17 responses.

AB - The significance of Th17 cells and IL-17A signaling in host defense and disease development has been demonstrated in various infection and autoimmune models. Additionally, the generation of Th17 cells is highly influenced by microbes. However, the specific bacterial components capable of shaping Th17 responses have not been well defined. The goals of this study were to understand how a bacterial toxin, cholera toxin (CT), modulates Th17-dominated response in isolated human CD4+ T cells, and what are the mechanisms associated with this modulation. CD4+ cells isolated from human peripheral blood were treated with CT. The levels of cytokine production and specific Th cell responses were determined by ELISA, Luminex assay, and flow cytometry. Along with the decreased production of other proinflammatory cytokines (IFN-γ , TNF-α, and IL-2), we found that CT could directly enhance the IL-17A production through a cAMP-dependent pathway. This enhancement is specific for IL-17A but not for IL-17F, IL-22, and CCL20. Interestingly, CT could increase IL-17A production only from Th17-committed cells, such as CCR6+ CD4+ T cells and in vitro-differentiated Th17 cells. Furthermore, we also demonstrated that this direct effect occurs at a transcriptional level because CT stimulates the reporter activity in Jurkat and primary CD4 + T cells transfected with the IL-17A promoter-reporter construct. This study shows that CT has the capacity to directly shape Th17 responses in the absence of APCs. Our findings highlight the potentials of bacterial toxins in the regulation of human Th17 responses.

UR - http://www.scopus.com/inward/record.url?scp=84885461709&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84885461709&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1301079

DO - 10.4049/jimmunol.1301079

M3 - Article

C2 - 24043897

AN - SCOPUS:84885461709

VL - 191

SP - 4095

EP - 4102

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 8

ER -