The role of heme oxygenase-1 on T cell activation, proliferation and homeostasis
Final Report Abstract
Heme oxygenase-1 (HO-1) was originally found as the rate-limiting enzyme in heme degradation. Besides its enzymatic function in heme metabolism, HO-1 shows distinctive immunomodulatory properties. A variety of stimuli, such as oxidative stress and a wide range of cytokines, induce the expression of HO-1. Altogether, higher HO-1 levels act in an anti-inflammatory and anti-apoptotic manner. Due to complexity of the immune system and a high distribution of HO-1 in divergent compartments, the exact mechanism of this immunosuppressive action is not elucidated yet. Through the funding of the project we elucidated for the first time the action of HO-1 on T cell activation and polarization. Basically it acts as a regulator and housekeeping molecule to modulate the immune responses. A line of evidences obtaining from HO-1 deficient mice demonstrated a paradox-effect of HO-1 on T cell activation. Endogenous HO-1 promotes the T cell activation, whereas exogenous HO- 1 suppresses the overreaction of T cells upon stimulation. In the T helper cell polarization, HO-1 has distinct functions, in which it suppresses the Th1 polarization via the interaction with T-bet. Administration of HO-1 protein protects the liver from acute Th1-dominant hepatitis in mice. In addition, HO-1 promotes the generation of the Treg cells, while it suppresses the polarization of Th17 cells. In conclusions, a study to further explore the action of HO-1 on promoting the Treg HO-1 would be of great potential to establish a HO-1-based the Treg cells therapy for clinical setting. A clinical phase one study could be established for organ protection in the near future.
