%0 Journal Article
%T Dendritic Cells from Crohn¡¯s Disease Patients Show Aberrant STAT1 and STAT3 Signaling
%A Janne K. Nieminen
%A Mirja Niemi
%A Taina Sipponen
%A Harri M. Salo
%A Paula Klemetti
%A Martti F£¿rkkil£¿
%A Jukka Vakkila
%A Outi Vaarala
%J PLOS ONE
%D 2013
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0070738
%X 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-¦Á-induced STAT3 phosphorylation and IFN-¦Á-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-¦Á-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-¦Ã-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 (¦Ñ = 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-¦Á-induced signaling in both DC subtypes, may contribute to the immunological dysregulation in CD patients.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0070738