• Mucosal immunology · Jul 2013

    C5a receptor signalling in dendritic cells controls the development of maladaptive Th2 and Th17 immunity in experimental allergic asthma.

    • I Schmudde, H A Ströver, T Vollbrandt, P König, C M Karsten, Y Laumonnier, and J Köhl.
    • Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
    • Mucosal Immunol. 2013 Jul 1; 6 (4): 807-25.

    AbstractThe pathways underlying dendritic cell (DC) activation in allergic asthma are incompletely understood. Here we demonstrate that adoptive transfer of ovalbumin-pulsed wild-type (wt) but not of C5a receptor-deficient (C5aR⁻/⁻) bone marrow (BM)-derived DCs (BMDCs) induced mixed T helper type 2 (Th2)/Th17 maladaptive immunity, associated with severe airway hyperresponsiveness, mucus production, and mixed eosinophilic/neutrophilic inflammation. Mechanistically, antigen uptake, processing, and CD11b expression were reduced in C5aR⁻/⁻ BMDCs. Further, interleukin (IL)-1β, -6, and -23 production were impaired resulting in reduced Th17 cell differentiation, associated with accelerated activated T-cell death in vitro and in vivo. Surprisingly, we found an increased frequency of CD11b(hi)CD11c(int)Gr1⁺F4/80⁺ cells, expressing arginase and nitric oxide synthase in C5aR⁻/⁻ BM preparations. Intratracheal administration of ovalbumin-pulsed wt DCs and sorted CD11b(hi)CD11c(int)Gr1⁺F4/80⁺ C5aR⁻/⁻ cells reduced Th2 immune responses in vivo. Together, we uncover novel roles for C5aR in Th17 differentiation, T-cell survival, and differentiation of a DC-suppressor population controlling Th2 immunity in experimental allergic asthma.

      Pubmed     Full text   Copy Citation  

      Add institutional full text...

    Notes

    hide…

What will the 'Medical Journal of You' look like?

Start your free 21 day trial now.

We guarantee your privacy. Your email address will not be shared.