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Subproject 2

T-cell-dependent regulation of autoreactive B cells in pemphigus

Summary

TP2.PNG

There is compelling evidence from experimental mouse models of PV including the HLA-transgenic mouse 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 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 both ex vivo in patients with PV and in mice by determining 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 and auto-ab formation 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 and in animal models 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, data of this project will help to define time-points at which interventional strategies may prevent the relapse of PV.

Applicants:

Prof Dr. Kamran Ghoreschi
Universitätsklinikum Tübingen
Universitäts-Hautklinik

Prof. Dr. Wolfgang Pfützner
Philipps-Universität Marburg
Fachbereich Medizin
Klinik für Dermatologie und Allergologie

Co-Applicant:

Dr. Christian Möbs
Philipps-Universität Marburg
Fachbereich Medizin
Klinik für Dermatologie und Allergologie