Do Foxp3+ Regulatory T Cells (Treg Cells) Play a Role in the Immunopathogenesis of Primary/Idiopathic Minimal Change Disease?
Figure 2
Dysfunctional Treg cells promoting a pathogenic “injury loop” in minimal change disease. (a) A numerical or functional imbalance between Foxp3+ Treg cells and Teff cells in response to undefined antigenic stimuli leads to systemic (e.g., at the lymph nodes) or local overproduction of cytokines, which could reach podocytes through filtration. (b) Direct toxicity of cytokines on podocytes further increases glomerular permeability and the release of proinflammatory molecules such as ATP. (c) If intrinsic or Treg cell-dependent regulatory mechanisms fail, persistent injury to podocytes leads to expression and shedding of CD80 molecules. Soluble CD80 molecules could diffuse back into the bloodstream and bind to CD28 on Teff cells, distantly or locally, sustaining continuous activation and synthesis of cytokines in a podocyte “injury loop.” (d) If instead CD39+Foxp3+ Treg cells manage to control Teff cells through the secretion of suppressive cytokines and soluble CD152 and by initiating extracellular ATP catabolism through CD39 on their surface, immune balance is restored and the “injury loop” is terminated.
