Cyclic AMP concentrations in dendritic cells induce and regulate Th2 immunity and allergic asthma

Jihyung Lee; Tae Hoon Kim; Fiona Murray; Xiangli Li; Sara S Choi; David H Broide; Maripat Corr; Jongdae Lee; Nicholas J G Webster; Paul A Insel; Eyal Raz

doi:10.1073/pnas.1417972112

Cyclic AMP concentrations in dendritic cells induce and regulate Th2 immunity and allergic asthma

Jihyung Lee, Tae Hoon Kim, Fiona Murray, Xiangli Li, Sara S Choi, David H Broide, Maripat Corr, Jongdae Lee, Nicholas J G Webster, Paul A Insel, Eyal Raz

Medical Sciences

Research output: Contribution to journal › Article › peer-review

37 Citations (Scopus)

Abstract

The inductive role of dendritic cells (DC) in Th2 differentiation has not been fully defined. We addressed this gap in knowledge by focusing on signaling events mediated by the heterotrimeric GTP binding proteins Gαs, and Gαi, which respectively stimulate and inhibit the activation of adenylyl cyclases and the synthesis of cAMP. We show here that deletion of Gnas, the gene that encodes Gαs in mouse CD11c(+) cells (Gnas(ΔCD11c) mice), and the accompanying decrease in cAMP provoke Th2 polarization and yields a prominent allergic phenotype, whereas increases in cAMP inhibit these responses. The effects of cAMP on DC can be demonstrated in vitro and in vivo and are mediated via PKA. Certain gene products made by Gnas(ΔCD11c) DC affect the Th2 bias. These findings imply that G protein-coupled receptors, the physiological regulators of Gαs and Gαi activation and cAMP formation, act via PKA to regulate Th bias in DC and in turn, Th2-mediated immunopathologies.

Original language	English
Pages (from-to)	1529-1534
Number of pages	6
Journal	PNAS
Volume	112
Issue number	5
Early online date	20 Jan 2015
DOIs	https://doi.org/10.1073/pnas.1417972112
Publication status	Published - 3 Feb 2015

Bibliographical note

ACKNOWLEDGMENTS.
The study was funded by NIH Grants HD12303, CA23100, and DK063491 (to N.J.G.W.); NIH Grants AI 38425, AI 70535, and AI 72115 (to D.B.); NIH Grants AI095623 and AI077989 (to E.R.); Veterans Affairs Grant I01BX000130 (to N.J.G.W.); and a grant from the Crohn’s and Colitis Foundation of America (to E.R.).

Keywords

Adoptive Transfer
Animals
Asthma
Cyclic AMP
Dendritic Cells
GTP-Binding Protein alpha Subunits, Gs
Hypersensitivity
Mice
Th2 Cells

Access to Document

10.1073/pnas.1417972112Licence: Unspecified

Fiona Murray
Person: Academic

Cite this

@article{d21fbba972594ee4b2962774fc04e62e,

title = "Cyclic AMP concentrations in dendritic cells induce and regulate Th2 immunity and allergic asthma",

abstract = "The inductive role of dendritic cells (DC) in Th2 differentiation has not been fully defined. We addressed this gap in knowledge by focusing on signaling events mediated by the heterotrimeric GTP binding proteins Gαs, and Gαi, which respectively stimulate and inhibit the activation of adenylyl cyclases and the synthesis of cAMP. We show here that deletion of Gnas, the gene that encodes Gαs in mouse CD11c(+) cells (Gnas(ΔCD11c) mice), and the accompanying decrease in cAMP provoke Th2 polarization and yields a prominent allergic phenotype, whereas increases in cAMP inhibit these responses. The effects of cAMP on DC can be demonstrated in vitro and in vivo and are mediated via PKA. Certain gene products made by Gnas(ΔCD11c) DC affect the Th2 bias. These findings imply that G protein-coupled receptors, the physiological regulators of Gαs and Gαi activation and cAMP formation, act via PKA to regulate Th bias in DC and in turn, Th2-mediated immunopathologies.",

keywords = "Adoptive Transfer, Animals, Asthma, Cyclic AMP, Dendritic Cells, GTP-Binding Protein alpha Subunits, Gs, Hypersensitivity, Mice, Th2 Cells",

author = "Jihyung Lee and Kim, {Tae Hoon} and Fiona Murray and Xiangli Li and Choi, {Sara S} and Broide, {David H} and Maripat Corr and Jongdae Lee and Webster, {Nicholas J G} and Insel, {Paul A} and Eyal Raz",

note = "ACKNOWLEDGMENTS. The study was funded by NIH Grants HD12303, CA23100, and DK063491 (to N.J.G.W.); NIH Grants AI 38425, AI 70535, and AI 72115 (to D.B.); NIH Grants AI095623 and AI077989 (to E.R.); Veterans Affairs Grant I01BX000130 (to N.J.G.W.); and a grant from the Crohn{\textquoteright}s and Colitis Foundation of America (to E.R.).",

year = "2015",

month = feb,

day = "3",

doi = "10.1073/pnas.1417972112",

language = "English",

volume = "112",

pages = "1529--1534",

journal = "PNAS",

issn = "0027-8424",

publisher = "NATL ACAD SCIENCES",

number = "5",

}

TY - JOUR

T1 - Cyclic AMP concentrations in dendritic cells induce and regulate Th2 immunity and allergic asthma

AU - Lee, Jihyung

AU - Kim, Tae Hoon

AU - Murray, Fiona

AU - Li, Xiangli

AU - Choi, Sara S

AU - Broide, David H

AU - Corr, Maripat

AU - Lee, Jongdae

AU - Webster, Nicholas J G

AU - Insel, Paul A

AU - Raz, Eyal

N1 - ACKNOWLEDGMENTS. The study was funded by NIH Grants HD12303, CA23100, and DK063491 (to N.J.G.W.); NIH Grants AI 38425, AI 70535, and AI 72115 (to D.B.); NIH Grants AI095623 and AI077989 (to E.R.); Veterans Affairs Grant I01BX000130 (to N.J.G.W.); and a grant from the Crohn’s and Colitis Foundation of America (to E.R.).

PY - 2015/2/3

Y1 - 2015/2/3

N2 - The inductive role of dendritic cells (DC) in Th2 differentiation has not been fully defined. We addressed this gap in knowledge by focusing on signaling events mediated by the heterotrimeric GTP binding proteins Gαs, and Gαi, which respectively stimulate and inhibit the activation of adenylyl cyclases and the synthesis of cAMP. We show here that deletion of Gnas, the gene that encodes Gαs in mouse CD11c(+) cells (Gnas(ΔCD11c) mice), and the accompanying decrease in cAMP provoke Th2 polarization and yields a prominent allergic phenotype, whereas increases in cAMP inhibit these responses. The effects of cAMP on DC can be demonstrated in vitro and in vivo and are mediated via PKA. Certain gene products made by Gnas(ΔCD11c) DC affect the Th2 bias. These findings imply that G protein-coupled receptors, the physiological regulators of Gαs and Gαi activation and cAMP formation, act via PKA to regulate Th bias in DC and in turn, Th2-mediated immunopathologies.

AB - The inductive role of dendritic cells (DC) in Th2 differentiation has not been fully defined. We addressed this gap in knowledge by focusing on signaling events mediated by the heterotrimeric GTP binding proteins Gαs, and Gαi, which respectively stimulate and inhibit the activation of adenylyl cyclases and the synthesis of cAMP. We show here that deletion of Gnas, the gene that encodes Gαs in mouse CD11c(+) cells (Gnas(ΔCD11c) mice), and the accompanying decrease in cAMP provoke Th2 polarization and yields a prominent allergic phenotype, whereas increases in cAMP inhibit these responses. The effects of cAMP on DC can be demonstrated in vitro and in vivo and are mediated via PKA. Certain gene products made by Gnas(ΔCD11c) DC affect the Th2 bias. These findings imply that G protein-coupled receptors, the physiological regulators of Gαs and Gαi activation and cAMP formation, act via PKA to regulate Th bias in DC and in turn, Th2-mediated immunopathologies.

KW - Adoptive Transfer

KW - Animals

KW - Asthma

KW - Cyclic AMP

KW - Dendritic Cells

KW - GTP-Binding Protein alpha Subunits, Gs

KW - Hypersensitivity

KW - Mice

KW - Th2 Cells

U2 - 10.1073/pnas.1417972112

DO - 10.1073/pnas.1417972112

M3 - Article

C2 - 25605931

SN - 0027-8424

VL - 112

SP - 1529

EP - 1534

JO - PNAS

JF - PNAS

IS - 5

ER -

Cyclic AMP concentrations in dendritic cells induce and regulate Th2 immunity and allergic asthma

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Profiles

Fiona Murray

Cite this