Download Name: - Welcome to the Dendritic Cell Symposium 2017

Name:
Diana Dudziak (PhD)
Address:
University Hospital of Erlangen
Research Campus Hartmannstrasse
Department of Dermatology
Laboratory of DC-Biology
Hartmannstr. 14
91052 Erlangen
Tel.:
+49 9131 85 39346
Fax:
+49 9131 85 39347
E-mail: [email protected]
Web link: http://www.hautklinik.ukerlangen.de/forschung-undlehre/grundlagenforschung/biologiedendritischer-zellen/
Interests:
DC subpopulations (mouse, human); antigen targeting; antigen processing; antigen presentation; T
cell tolerance; immunity, inflammation (TLR-ligands); immune regulation; tumor
Techniques:
Molecular Biology, Microarrays, 18 color flow cytometry, 6 color confocal immunofluorescence
analysis, antigen targeting
Model systems available:
Transgenic/knock-in mice: OT-I, OT-II, OT-II-GFP, DO11.10, GFP, CFP, CD11c-YFP, CD11c-DTR,
BRAF/PTEN, Trisomy: DP10, DP16, Dp17
K.O. mice: TLR (3,4,5,9), MyD88, TRIF, b2m, Tap1, t-bet, CCR2, CCR7, diverse FcγRs, BATF3,
Cathepsin S, CD14, Zbtb46, MMR, CD40, IFNaR, LMP2/LMP7/Mecl1, Rag-1, DCIR1
Title: Dendritic cells in mice and men
Dendritic cells (DCs) are important cells for the presentation of antigens. In dependence of
the surroundings, DCs are capable of presentation of antigen in an immature or mature state.
Therefore, immune responses are tightly regulated by the DCs, as T cells recognizing
peptide MHC-complexes on immature DCs undergo deletion or anergic responses whereas
T cells recognizing pMHC complexes on mature DCs undergo proliferative responses
leading to T cell memory. Our lab is focusing on understanding how DC subpopulations
regulate these T cell responses. By antigen targeting using recombinant antigen-conjugated
antibodies directed against endocytosis receptors specifically expressed on DC
subpopulations we could show that antigen-loaded CD11c+CD8- DCs induce a pronounced
CD4 helper T cell response whereas antigen loaded CD11c+CD8+ induce a prominent CD8 T
cell response in C57BL/6 mice. We further found that CD11c+CD8- splenic DCs express
higher levels of molecules important for antigen processing to MHC-II whereas CD11c+CD8+
DCs express higher levels of molecules important for antigen processing to MHC-I, thus
demonstrating a specialization of the different DC subpopulations in the induction of immune
responses in the steady state (Dudziak et al., Science, 2007).
Currently, we are investigating 1. whether the induced immune responses are suitable for the
rejection of tumor cells (Neubert et al., 2014); 2. what is happening with the induction of
immune responses if a variety of antigen presenting cells are targeted with antigens
(Lehmann et al. in revision); 3. how the antigen presenting abilities are changing in the
different DC subpopulations after immune stimulation (Yamazaki et al., 2008; Baranska et
al., under review), and 4. how to translate our knowledge from the murine into the human
system (Heidkamp et al., 2010; Eissing et al., 2014; Heidkamp et al., in revision; Heger et al.,
in preparation)? With gaining knowledge about functions of DC subpopulations in mouse and
man and how to direct immune responses in either tolerogenic or immunogenic directions it
might be possible to develop new immunotherapeutic options in the fight against cancer and
autoimmunity.