hIgD-Fc-Ig fusion protein regulate T cell functions by inhibiting TCR signaling pathway in adjuvant arthritis rats

Abstract

Abstract hIgD-Fc-Ig is a fusion protein that competes to bind IgD receptors, it remains unclear whether hIgD-Fc-Ig can regulate T cell function by regulating TCR signaling pathway in the treatment of adjuvant arthritis rats. In vivo, AA rats were treated with hIgD-Fc-Ig fusion protein and Etanercept for 28 days, then the overall indexes of AA rats, the severity of the pathology, the proliferation of spleen and thymus, the changes of blood flow signal in the knee joints as well as bone erosion of ankle joints were detected. Flow cytometry was used to detect the changes of peripheral blood and spleen T cell subsets. In vitro, rat spleen T cells or Jurkat cells were treated by IgD, and Lck inhibitor (PP1) and CD3ε siRNA were used to observe the function of IgD and hIgD-Fc-Ig on TCR and its downstream protein expression. The results showed that hIgD-Fc-Ig fusion protein had a obvious therputic effect on adjuvant arthritis rats, which could improve overall index, pathological status, the proportion of T cell subsets and other indicators. In addition, hIgD-Fc-Ig inhibited the expression of TCR and its downstream related proteins in rat spleen T cells or Jurkat cells. Which provided evidence that hIgD-Fc-Ig fusion protein could alleviate the symptoms of AA rats and regulate T cells through TCR-Lck-Erk signaling pathway. In a word, activated TCR signaling pathway leads to T cell activation which could be inhibited by hIgD-Fc-Ig fusion protein through regulating TCR signaling pathway. hIgD-Fc-Ig might be an immunomodulatory drug with anti-inflammatory effects.