Delineation of pathogenic plasma cell subsets

• Applicant: Andreia Lino, Ph.D.
• Subject Area: Rheumatology
• Term: from 2019 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 423502701

Plasma cells (PCs) have the unique capacity of producing antibodies (Abs), which are the effectors of the humoral response against virtually all microbes and toxins, but also to self-antigens participating in the development of autoimmune diseases. In the last years, it became clear that PCs contribute in more ways than just to secreting Abs, as their cytokine production, namely interleukin (IL)-10+LAG3+ PCs or IL-35+ PCs, partly complement activation or their interaction with other cells are critical. Thus, PCs represent a heterogeneous immune compartment composed of several subsets with different functions in immunity and immunoregulation. These findings suggest that certain characteristics, i.e., surface markers of disease-specific PC subsets allow targeting pathogenic PCs with high selectivity in various autoimmune diseases. Translational research indicates the presence of similar PC subsets in human and mouse. In this project and based on our previous work, we aim to 1) define subsets of pathogenic and immunoregulatory PCs and the function-type of PC subsets in the context of systemic lupus erythematosus (SLE); 2) define the role of microbiota as driver of selective PC expansion in the context of SLE; 3) selective targeting of pathogenic PC by pharmacologic intervention(s). The overarching concept of this proposal is that there are several subsets of PCs with a distinct function. Certain subsets are pathogenic while others are immunoregulatory or protective which the project will address and translate into selective targeting pathogenic PC. This can be achieved either directly or indirectly through the control of certain bacteria species. The proposal will provide the basis that selective targeting of pathogenic PC in SLE has potential to modify disease outcome.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Thomas Dörner