Cyclic AMP Concentrations in Dendritic Cells Induce and Regulate Th2 Immunity and Allergic Asthma

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2015 Jan 22

PMID 25605931

Citations 31

Authors

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

Affiliations

Soon will be listed here.

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.

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