Project Details
Projekt
T-cell-dependent regulation of autoreactive B cells in pemphigus
Applicants
Professor Dr. Kamran Ghoreschi; Dr. Christian Möbs
Subject Area
Dermatology
Immunology
Immunology
Term
from 2016 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 289113135
The generation of autoreactive, Dsg-specific IgG autoantibodies by B cells is a pivotal point in the pathogenesis of pemphigus. Since activation of B lymphocytes requires help of T cells, the T/B cell cross-talk with regard to regulation and maintenance of autoantibody formation is of major interest. In previous studies, we analyzed T and B cell subsets in peripheral blood as well as cytokine profiles in the skin of pemphigus patients. Our results revealed a characteristic disease- and therapy-related distribution of distinct cell populations and cytokine patterns.Thus, we will extend our studies focusing on the role of follicular T (Tfh) cells and T cells with a regulatory phenotype (Treg and Tfr cells) in T/B cell interaction and antibody production, respectively. We will perform a detailed phenotypic evaluation of the different T cell populations by multiparametric analysis of transcription factors and surface molecules. Furthermore, we will analyze the impact of the IL-17-pathway on Tfh cell-induced antibody production. Since it has been shown that T/B cell interactions not only take place in germinal centers as secondary lymphoid organs but also in so-called tertiary lymphoid organs (TLOs) established directly in the diseased tissues. Therefore, we will assess the tissue-specific distribution of cells involved in the T/B cross-talk in the inflammatory environment of pemphigus skin lesions. Furthermore, by utilizing biological response modifiers we will try to modulate intracellular signaling pathways to elucidate their potential impact on both the above-mentioned T cell subsets and autoantibody production in pemphigus. The proposed experiments will thus allow to better understand the cross-talk of T and B cells in pemphigus helping to identify new targets for treatment of the autoimmune disease.
DFG Programme
Research Units
Co-Investigator
Professor Dr. Wolfgang Pfützner
