Pollen metabolome analysis reveals adenosine as a major regulator of dendritic cell–primed TH cell responses - 10/08/11
, Agnes Fekete, PhD b, , Xin Zhang a, Isabelle Beck, MS a, Cornelia Blume, PhD a, Johannes Ring, MD c, Carsten Schmidt-Weber, PhD a, Heidrun Behrendt, MD a, Philippe Schmitt-Kopplin, PhD b, d, Claudia Traidl-Hoffmann, MD a, c, ⁎ 
Reprint requests: Claudia Traidl-Hoffmann, MD, Department of Dermatology and Allergy, Technische Universität München, Biedersteinerstr. 29. 80802 Munich.Abstract |
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 TH2-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 TH 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 TH 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 TH1 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.
Il testo completo di questo articolo è disponibile in PDF.Key words : Dendritic cells, immunomodulation, adenosine, pollen, allergy
Abbreviations used : ADA, APE, cAMP, CFSE, DC, FITC, Foxp3, PE, SPE, Treg, UPLC, UPLC-PDA, UPLC–TOF-MS
Mappa
| Supported by the Faculty of Medicine of the Technische Universität München (S.G. and C.T.-H.), the Deutsche Forschungsgemeinschaft (C.T.-H.), and the Christine-Kühne-Stiftung (CK-Care). |
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| Disclosure of potential conflict of interest: The authors have declared they have no conflict of interest. |
Vol 127 - N° 2
P. 454 - Febbraio 2011 Ritorno al numero
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