Project Details
Projekt
Role of dendritic cell subsets in glomerulonephritis
Applicant
Professor Dr. Christian Kurts
Subject Area
Nephrology
Term
from 2009 to 2015
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 101885864
We recently reported that activation of kidney dendritic cells (kDCs) drives progression of nephrotoxic glomerulonephritis (NTN), a model of human crescentic GN (cGN), by mechanisms involving chemokine-mediated recruitment of immune effector cells. By contrast, immature kDCs attenuated cGN by chemokine-mediated recruitment of immunosuppressive natural killer T cells (NKT cells) and regulatory T cells (Tregs,) whose function surprisingly depended on the transcription factor NF-κB. Furthermore, we found that Batf3-dependent kDCs, a small subset of DCs characterized in the kidney by CD103 expression, possess a surprisingly strong protective functionality in NTN. In the next funding period, we wish to clarify the mechanisms underlying the function of Batf3-dependent and -independent kDCs. We will 1. Study the role of Batf3-dependent kDCs on the systemic Th1 cell immune response against the kidney; 2. Distinguish between effects of Batf3-dependent and -independent kDCs in NTN, with a particular focus on potential interactions with suppressive iNKT cells and Tregs; 3. Clarify how kidney DC function turns pro-inflammatory in chronic NTN, by distinguishing whether the ratio between protective and pro-inflammatory DCs shifts towards the latter or whether protective DCs mature and lose their protective functionality, for example through NF-κB; and 4. Clarify which kDC subsets migrate to the renal lymph node in NTN. We expect that knowledge of the roles of DCs and their regulatory functions in cGN may facilitate developing new DC-targeted therapies for GN.
DFG Programme
Clinical Research Units
