Treg/Th17 Imbalance And Its Effect On Myeloid Megakaryoctye In Immune Thrombocytopenia

Primary immune thrombocytopenia (ITP) is an organ-specific autoimmune disease, characterized with decreased platelet count and increased bleeding risk. Multiple immune mechanisms take part in the pathogenesis, including the accelerating destruction of platelet by auto-antibodies and by auto-reactive T cells, and ineffective thrombocytopoeisis caused by auto-antibodies and by CD8+T cells. CD4+T cells play an important role in the development of ITP, for they help B cells to produce auto-antibodies, as well as secrete many pro-inflammatory cytokines. Meanwhile, Tregs is the other key factor in the pathogenesis. Recent studies showed that the immune regulatory Tregs was tightly related with the pro-inflammatory Th17, which takes part in many autoimmune diseases. They shared a common precursor cell, which could develop into either type of cells depending on the environmental cytokines. We followed ITP patients in the long-term to found that the balance of Treg and Th17 skewed toward Th17 when ITP occurred and that the balance recovered when the disease remitted. The number of Tregs at diagnosis had a prognostic role.Further study into the function of Tregs showed that Tregs’two work modes:in the physiology state, Tregs suppressed T effector cells (Teffs) via cell-to-cell contact; in the inflammatory conditions on the contrary; they shed suppression by secreting regulatory cytokines, such as IL-10, to unable or kill Teffs. IL-10 is an important regulatory cytokine, which could be induced by IFN-y to inhibit Thl, Th17, and IFN-y+IL-17+ Th cells directory. Several studies argued that IL-10-producing Foxp3+Tregs could by therapeutic in several autoimmune diseases. In ITP, we demonstrated that although IL-10 massed inside Tregs, they secreted insufficient IL-10 to inhibit the unduly activated Teffs. In the meantime, the activated Teffs may take part in the pathogenesis, which needs to be testified.Megakaryocyte is the only producer of platelet, its dysfunction attributes to the decreasing platelet. Solid proofs showed that plasma of ITP patients, and CD8+T cells caused deficient megakaryocyte production, abnormal maturation, and limited thrombocytopoiesis. However, it has no report dealing with whether CD4+T cells influence the megakaryocyte. A murine model study demonstrated that CD8+T cells induced ITP dependent on CD4+T cells. The study aroused our interest in the effect of CD4+T cells on the megakaryocyte. Thus, we separated stem cells from the bone marrow of ITP patients to culture them under megakaryocyte condition. The results showed that CD4+T cells may suppress the production of megakaryocyte and platelet. Besides, we discovered that the stem cells of ITP patients may have instinct defect to impede the megakaryocyte production and maturation, and to put off the platelet formation. However, to confirm the deduction needed more samples to be performed.