β2-adrenergic receptor agonist corrects immune thrombocytopenia by reestablishing the homeostasis of T cell differentiation

The sympathetic nerve is known to regulate immune responses in autoimmunity. Aberrant T cell immunity plays a vital role in immune thrombocytopenia (ITP) pathogenesis. The spleen is the primary site of platelet destruction. However, little is known whether and how splenic sympathetic innervation and neuroimmune modulation contribute to ITP pathogenesis.To determine the sympathetic distribution in the spleen of ITP mice and the association between splenic sympathetic nerves and T cell immunity in ITP development, and to evaluate the treatment potential of β2-adrenergic receptor (β2-AR) in ITP.Chemical sympathectomy was performed in an ITP mouse model with 6-hydroxydopamine and treated with β2-AR agonists to evaluate the effects of sympathetic denervation and activation.Decreased sympathetic innervation in the spleen of ITP mice was observed. Significantly increased percentages of Th1 and Tc1 cells and reduced percentages of regulatory T cells (Tregs) were also observed in ITP mice with chemical sympathectomy (ITP-syx mice) relative to mice without sympathectomy (controls). Expression of genes associated with Th1, including IFN-γ and IRF8, was significantly upregulated, whereas genes associated with Tregs, including Foxp3 and CTLA4, were significantly downregulated in ITP-syx mice compared with controls. Furthermore, β2-AR restored the percentage of Tregs and increased platelet counts at days 7 and 14 in ITP mice.Our findings indicate that decreased sympathetic distribution contributes to ITP pathogenesis by disturbing the homeostasis of T cells and that β2-AR agonists have potential as a novel treatment for ITP.