Dendritic cells are involved in the resolution of inflammation by IVIg in arthritis
LEHMANN C. 1,2,3, AMON L. 1, SEICHTER A. 1, BRÜCKNER C. 5, ALTMANN L. 5, HEGER L. 1,2,3, RAVECHT J. 6, NIMMERJAHN F. 5, DUDZIAK D. 1,2,3,4
1 Laboratory for DC-Biology, Dermatology, University Hospital Erlangen, Erlangen, Germany; 2 Medical Immunology Campus Erlangen (MICE), Erlangen, Germany; 3 German Center for Immunotherapy (DZI), Erlangen, Germany; 4 Institute for Immunology, University Hospital Jena, Jena, Germany; 5 Department of Biology, Chair of Genetics, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany; 6 Leonard Wagner Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, United States
Intravenous immunoglobulins (IVIg) are a mixture of mainly IgG antibodies isolated from >10,000 donors. IVIg is applied not only in low doses as a supplementation therapy for patients lacking antibodies (e.g., after bone marrow transplantation) but is also used in high doses to treat various autoinflammatory diseases. Although its potential is known and used for a long time, the mode of action is still not fully resolved. Dendritic cells (DCs) are important antigen presenting cells (APCs) and induce immune responses, but also preserve peripheral tolerance. In preventive studies of KBxN serum transfer arthritis, it has been proposed that IVIg-loaded monocyte-derived DCs (BMDCs) can replace IVIg therapy. However, primary DCs as well as their use in therapeutic systems has not been investigated. Here, we tested the potential of IVIg-loaded primary DC subsets for the resolution of inflammation after the induction of KBxN serum transfer arthritis. We found that the various murine subpopulations of DCs differ in their functional properties. Therefore, we also investigated, if the resolution of inflammation is dependent on a specific subset or if multiple DC subsets are involved. During our studies, we used different DC knock-out models, such as CD11c-Cre x Irf4fl/fl and BatF3-/- mice. This project was partly funded by the DFG (CRC1181-TPA7) and intramural funding (IZKF-A87).