Project Details
Projekt
T cells as regulative element during the onset of autoantibody-mediated Arthritis
Applicant
Professor Dr. Gerhard Krönke
Subject Area
Rheumatology
Term
from 2019 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 405969122
Autoantibodies such as anti-citrullinated protein antibodies (ACPA) are considered to essentially contribute to the pathogenesis of rheumatoid arthritis (RA). However, formation of ACPA can precede clinical disease and joint inflammation for many years and ACPA levels do not necessarily correlate with disease activity, suggesting that other yet to be defined checkpoints control onset of autoantibody-mediated joint inflammation in RA. Our published data from the first funding period of PANDORA identified tissue-resident anti-inflammatory Cx3cr1+ macrophages that form protective barriers around synovial joints and prevent onset of autoantibody-mediated joint inflammation under homeostatic conditions. Our preliminary data show that autoreactive T cells interact with such barrier-forming synovial Cx3cr1+ macrophages prior to onset of inflammation thereby lowering the local inflammatory threshold and “licensing” the synovial tissue for autoantibody-induced arthritis via production of granulocyte-macrophage colony-stimulating factor (GM-CSF). During the second funding period, we thus seek to decipher the GM-CSF-dependent molecular mechanisms and responding synovial cell types that enable onset of autoantibody-induced arthritis and additionally plan to determine the relevance of the underlying processes for human RA.
DFG Programme
Research Units
