PuSH - Publication Server of Helmholtz Zentrum München

Gilles, S. ; Fekete, A. ; Zhang, X. ; Beck, I. ; Blume, C. ; Ring, J.* ; Schmidt-Weber, C.B. ; Behrendt, H. ; Schmitt-Kopplin, P. ; Traidl-Hoffmann, C.

Pollen metabolome analysis reveals adenosine as a major regulator of dendritic cell-primed TH cell responses.

J. Allergy Clin. Immunol. 127, 454-461 (2011)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
BACKGROUND: Water-soluble components from pollen modulate dendritic cell (DC) functions, such as IL-12 secretion and 3'-5'-cyclic adenosine monophosphate (cAMP) signaling and migration, possibly contributing to the establishment of a T(H)2-dominated immune response against pollen. Because these effects could not solely be attributed to the previously identified pollen-associated lipid mediators, the pollen metabolome was analyzed for candidate immunomodulatory substances. OBJECTIVE: We sought to perform an analysis of the effect of pollen-associated adenosine on DC function and T(H) cell differentiation. METHODS: Fractions of aqueous pollen extracts (APEs) were generated by means of ultrafiltration and were subjected simultaneously to biological tests and metabolome analysis (ultra-high-resolution mass spectrometry) and ultraperformance liquid chromatography. Effects of pollen-derived adenosine on monocyte-derived DC cAMP signaling, cytokine response, and capacity to differentiate T(H) cells were studied. RESULTS: The less than 3-kd fraction of APEs comprised thousands of substances, including adenosine in micromolar concentrations. Pollen-derived adenosine mediated A₂ receptor-dependent induction of cAMP and inhibition of IL-12p70 in DCs. APEs digested with adenosine deaminase failed to mediate IL-12 inhibition. DCs of nonatopic donors exposed to APEs showed an adenosine-dependent reduced capacity to differentiate T(H)1 cells and an enhanced capacity to induce regulatory T cells and IL-10. DCs of atopic donors failed to induce IL-10 but instead induced IL-5 and IL-13. CONCLUSION: This study identifies adenosine out of thousands of metabolites as a potent immunoregulatory substance in pollen. It acts on the level of the DC, with differential effects in atopic and nonatopic donors.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Keywords Dendritic cells; immunomodulation; adenosine; pollen; allergy
ISSN (print) / ISBN 0091-6749
e-ISSN 1097-6825
Journal The journal of allergy and clinical immunology
Quellenangaben Volume: 127, Issue: 2, Pages: 454-461 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam [u.a.]
Reviewing status Peer reviewed
Institute(s) Institute of Lung Health and Immunity (LHI)
Institute of Epidemiology (EPI)
Institute of Ecological Chemistry (IOEC)