The neuropeptide calcitonin gene‐related peptide affects allergic airway inflammation by modulating dendritic cell function

Rochlitzer, Sabine; Veres, TZ; Kühne, Katharina; Prenzler, Frauke; Pilzner, Carolin; Knothe, S.; Winkler, Carla; Lauenstein, Hans-Dieter; Willart, Monique; Hammad, Hamida; Müller, Meike; Krug, Norbert; Lambrecht, Bart N.; Braun, Armin

doi:10.1111/j.1365-2222.2011.03822.x

Cited by 78 publications

(62 citation statements)

References 58 publications

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“…These data, combined with our previous observations that show induction of Th17 response (16) by high levels of cAMP in DC mostly via Gαs activation, indicate that in addition to PRR, signaling via regulators of cAMP levels, Gαs, and Gαi in CD11c + DC (and not in CD11c − ILC2 cells) (38) contributes to Th subset differentiation. Furthermore, the current findings help explain certain previous data, for example evidence that CGRP, a neuronally derived peptide that binds to a Gs-coupled receptor, can be an antiinflammatory mediator in the setting of allergic airway inflammation (39). Although Gnas ΔCD11c mice are atopic from an early age ( Fig.…”

Section: Discussionsupporting

confidence: 68%

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

Lee¹,

Kim

Murray

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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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.cAMP | dendritic cells | Th2 | PKA | asthma

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Section: Discussionsupporting

confidence: 68%

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

Lee¹,

Kim

Murray

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Bronchoalveolar lavage was performed by instillation of 0.8 ml ice-cold PBS twice as described before [10]. The BALF was centrifuged (320 × g, 10 min, 4°C) and the supernatants were removed.…”

Section: Methodsmentioning

confidence: 99%

Allergic airway inflammation induces the migration of dendritic cells into airway sensory ganglia

Rochlitzer

Fischer

et al. 2014

Respir Res

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BackgroundA neuroimmune crosstalk between dendritic cells (DCs) and airway nerves in the lung has recently been reported. However, the presence of DCs in airway sensory ganglia under normal and allergic conditions has not been explored so far. Therefore, this study aims to investigate the localisation, distribution and proliferation of DCs in airway sensory ganglia under allergic airway inflammation.MethodsUsing the house dust mite (HDM) model for allergic airway inflammation BALB/c mice were exposed to HDM extract intranasally (25 μg/50 μl) for 5 consecutive days a week over 7 weeks. With the help of the immunohistochemistry, vagal jugular-nodose ganglia complex (JNC) sections were analysed regarding their expression of DC-markers (MHC II, CD11c, CD103), the neuronal marker PGP 9.5 and the neuropeptide calcitonin gene-related peptide (CGRP) and glutamine synthetase (GS) as a marker for satellite glia cells (SGCs). To address the original source of DCs in sensory ganglia, a proliferation experiment was also carried in this study.ResultsImmune cells with characteristic DC-phenotype were found to be closely located to SGCs and vagal sensory neurons under physiological conditions. The percentage of DCs in relation to neurons was significantly increased by allergic airway inflammation in comparison to the controls (HDM 51.38 ± 2.38% vs. control 28.16 ± 2.86%, p < 0.001). The present study also demonstrated that DCs were shown to proliferate in jugular-nodose ganglia, however, the proliferation rate of DCs is not significantly changed in the two treated animal groups (proliferating DCs/ total DCs: HDM 0.89 ± 0.38%, vs. control 1.19 ± 0.54%, p = 0.68). Also, increased number of CGRP-positive neurons was found in JNC after allergic sensitisation and challenge (HDM 31.16 ± 5.41% vs. control 7.16 ± 1.53%, p < 0.001).ConclusionThe present findings suggest that DCs may migrate from outside into the ganglia to interact with sensory neurons enhancing or protecting the allergic airway inflammation. The increase of DCs as well as CGRP-positive neurons in airway ganglia by allergic airway inflammation indicate that intraganglionic DCs and neurons expressing CGRP may contribute to the pathogenesis of bronchial asthma. To understand this neuroimmune interaction in allergic airway inflammation further functional experiments should be carried out in future studies.

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“…In fact, experimental data suggest that neuromediators might cooperate with immune cells during the latter phases of inflammation to mediate tissue repair and restore tissue homeostasis 91,92 . For instance, CGRP has been shown to have anti-inflammatory actions: it can inhibit DC maturation, migration to the lymph nodes as well as antigen presentation and prevent mast cell degranulation 84,93,94 . Moreover, CGRP can inhibit mouse T cell proliferation and regulate lymphocyte function in several ways 87,93,95 .…”

Section: Actions Of Neuropeptides On Immune Cellsmentioning

confidence: 99%

Crosstalk between the nociceptive and immune systems in host defence and disease

2015

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Nociceptors and immune cells both protect the host from potential threats to homeostasis. There is growing evidence for bidirectional signalling between these two systems, and the underlying mechanisms are beginning to be elucidated. An understanding is emerging of how both the adaptive and innate immune systems can activate and sensitize nociceptors, and, reciprocally, how nociceptors modulate immune cells. In this Review, we discuss how these interactions can be adaptive and useful to the organism but also consider when such signalling might be maladaptive and pathophysiological, contributing to immune-mediated diseases and persistent pain states.

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The neuropeptide calcitonin gene‐related peptide affects allergic airway inflammation by modulating dendritic cell function

Cited by 78 publications

References 58 publications

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

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

Allergic airway inflammation induces the migration of dendritic cells into airway sensory ganglia

Crosstalk between the nociceptive and immune systems in host defence and disease

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