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TP2: T-cell-dependent regulation of autoreactive B cells in pemphigus
Summary
There is compelling evidence from experimental mouse models of PV including the HLA-transgenic mice that the pathogenesis of PV is dependent on the interplay of T and B cells. For instance, the generation of Dsg3-specific, pathogenic IgG auto-ab requires the activation of autoreactive B cells which is initiated by autoreactive T cells. In this project, different subpopulations of T cells (Th, Tf, and Treg cells), as well as B cells, will be studied ex vivo in patients with PV. Both peripheral blood and skin are examined to determine the expression of surface receptors, transcription factors, signaling molecules, and cytokine secretion.
To functionally address T/B cell interaction, the impact of Th and Tf cell subsets on activation of autoreactive B cells, their formation of auto-ab, and vice versa will be investigated. In parallel, the developmental stages of peripheral B cell populations will be studied in patients with active or remittent PV. Furthermore, PV patients in remission will be followed longitudinally to determine whether changes in distinct B cell subsets are associated with a clinical relapse of PV and whether this is accompanied by altered T cell function.
The proposed experiments in PV patients will thus allow i) to better understand the T/B cell interaction in PV pathogenesis, ii) to characterize the disease-relevant T cell subsets and the prominent B cell phenotype iii) and to identify new targets for treatment of PV. Furthermore, the data of this project will help to define time points at which interventional strategies may prevent the relapse of PV.
Contact
Prof. Dr. Kamran Ghoreschi
Project leader TP2
Charité - Universitätsmedizin Berlin
Charitéplatz 1
D-10117 Berlin
Tel +49 30 450 518 062
Fax +49 30 450 518 911
E-Mail: kamran.ghoreschi@charite.de
Dr. Christian Möbs
Project leader TP2
Klinik für Dermatologie und Allergologie
Philipps-Universität Marburg
Baldingerstraße
D-35043 Marburg
Tel +49 6421 58 61405
Fax +49 6421 58 64824
E-Mail: moebs@med.uni-marburg.de
Prof. Dr. Wolfgang Pfützner
Co-leader TP2
Klinik für Dermatologie und Allergologie
Philipps-Universität Marburg
Baldingerstraße
D-35043 Marburg
Tel +49 6421 58 62488
Fax +49 6421 58 62883
E-Mail: Wolfgang.Pfuetzner@med.uni-marburg.de
