European Hematology Association - Restoration of T Helper Cell Imbalance in Immune Thrombocytopenia by β2-Adrenergic Receptor Agonists
THE HAGUE, Netherlands, June 11, 2021 /PRNewswire/ -- Immune thrombocytopenia (ITP) is a disease manifesting as a low platelet count in which dysregulation of T helper (Th) cells play a central role. Th1 and Th17 subsets are associated with the production of autoantibodies against platelets and restoration of the immune imbalance of Th cells results in clinical improvement. Recent studies have demonstrated the presence of β2-adrenergic receptor (β2-AR) as the primary adrenergic receptor on immune cells and shown that the nervous system can directly modulate Th cell polarization. Here, we explored the regulation of the sympathetic nervous system on Th cell polarization and the role of β2-AR signaling in immune cell development and pathways during ITP.
We employed an active ITP mouse model and chemically depleted the sympathetic nerves by administration of 6-OHDA (sympathectomy). Sympathectomized ITP mice exhibited a significantly longer platelet recovery time, lower survival, and expressed more Th1 genes than non-sympathectomized mice. We then injected the mice with terbutaline, a β2-AR agonist, to stimulate β2-AR signaling and found that platelet counts improved in both groups of mice. Furthermore, terbutaline restored the immune imbalance of Th cells to control levels. Subsequently, we isolated peripheral blood mononuclear cells from ITP patients found terbutaline treatment have no effect on the proliferation of both CD4+t cells and CD8+t cells. Interestingly, stimulation of ITP patient cells with terbutaline inhibited the differentiation of Th1 cells while inducing the differentiation of Th2 and regulatory T cells. In summary, impaired sympathetic innervation and the resulting Th dysregulation is important for directing the pathogenesis of ITP, which can be reversed by terbutaline treatment. This highlights a novel therapeutic approach for the treatment of ITP.
The results of this study will be presented by Professor Zhang in the Presidential Symposium.
Presenter: Professor Xiao-Hui Zhang
Affiliation: Peking University People's Hospital, Beijing, China
Abstract: #S104 A Β2 ADRENERGIC RECEPTOR AGONIST CORRECTS DYSREGULATED POLARIZATION OF T HELPER CELLS IN PRIMARY IMMUNE THROMBOCYTOPENIA
About the EHA Congress: Every June, EHA organizes its Annual Congress in a major European city. This year, due to the persisting COVID19 pandemic, EHA organizes a virtual Congress for the second time. The Congress is aimed at health professionals working in or interested in the field of hematology.
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