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Plos One : Dendritic Cells from Crohn’s Disease Patients Show Aberrant Stat1 and Stat3 Signaling, Volume 8

By Chamaillard, Mathias

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Book Id: WPLBN0003946373
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos One : Dendritic Cells from Crohn’s Disease Patients Show Aberrant Stat1 and Stat3 Signaling, Volume 8  
Author: Chamaillard, Mathias
Volume: Volume 8
Language: English
Subject: Journals, Science, Medical Science
Collections: Periodicals: Journal and Magazine Collection (Contemporary)
Publication Date:
Publisher: Plos


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Chamaillard, M. (n.d.). Plos One : Dendritic Cells from Crohn’s Disease Patients Show Aberrant Stat1 and Stat3 Signaling, Volume 8. Retrieved from

Description : Abnormalities of dendritic cells (DCs) and STAT proteins have been reported in Crohn’s disease (CD). Studies on JAK/STAT signaling in DCs are, however, lacking in CD. We applied a flowcytometric single-cell-based phosphoepitope assay to evaluate STAT1 and STAT3 pathways in DC subsets from CD patients. In addition, circulating DC counts were determined, together with the activation-related immunophenotype. We found that IL-6- and IFN-a-induced STAT3 phosphorylation and IFN-a-induced STAT1 phosphorylation were impaired in plasmacytoid DCs (pDCs) from CD patients (P = 0.005, P=0.013, and P=0.006, respectively). In myeloid DCs (mDCs), IFN-a-induced STAT1 and STAT3 phosphorylation were attenuated (P,0.001 and P=0.048, respectively), but IL-10-induced STAT3 phosphorylation was enhanced (P = 0.026). IFN-c-induced STAT1 signaling was intact in both DC subtypes. Elevated plasma IL-6 levels were detected in CD (P = 0.004), which strongly correlated with disease activity (r = 0.690, P,0.001) but not with IL-6-induced STAT3 phosphorylation. The numbers of pDCs and BDCA3+ mDCs were decreased, and CD40 expression on CD1c+ mDCs was increased in CD. When elucidating the effect of IL-6 signaling on pDC function, we observed that IL-6 treatment of healthy donor pDCs affected the maturation of and modified the T-cell priming by pDCs, favoring Th2 over Th1 type of response and the expression of IL-10 in T cells. Our results implicate DC signaling in human CD. Reduced IL-6 responsiveness in pDCs, together with the attenuated IFN-ainduced signaling in both DC subtypes, may contribute to the immunological dysregulation in CD patients


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