Project B1

T cells as regulative element during the onset of autoantibody-mediated arthritis

Our published data from the first funding period of PANDORA identified tissue-resident antiinflammatory 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 granulocytemacrophage 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.

2019-2022 (1st funding period):

Checkpoints and mechanisms that control the onset of autoantibody-mediated inflammatory diseases such as RA remain incompletely understood. Our preliminary data show that collagen II (CII)-specific autoreactive T cells essentially control the onset of arthritis that develops upon passive transfer of CII-specific arthritogenic autoantibodies. Although underlying molecular mechanisms remain elusive, our preliminary findings suggest that autoreactive IL-23-dependent T cells “license” the joint for autoantibody-induced inflammation and that T cells and autoantibodies act in a synergistic and antigen-specific manner.

Skizze Gelenk. Aktivierung von Th17 Zellen durch B Zellen. — transition from autoimmunity to joint inflammation

The aim of this project is to dissect and understand underlying events and in particular to address a role of specific T cell subsets in regulating the trafficking and activity of autoantibodies to and within the joint as well as to determine the relevance of this phenomenon for human RA.