Thymic stromal lymphopoietin (TSLP), induced via OX40-ligand (OX40L) expressed on dendritic cells (DCs), is a key player in the induction of the T helper (Th)2 cell-mediated allergic cascade. Therefore, the TSLP-DC-OX40L axis might be the principal pathway in the inflammatory cascades in allergic diseases. Microparticles (MPs) are small membrane vesicles released from many different cell types by exocytotic budding of the plasma membrane in response to cellular activation or apoptosis. Elevated levels of platelet-derived MPs, endothelial cell-derived MPs, and monocyte-derived MPs in venous and arterial beds have been reported in almost all thrombotic diseases. However, the clinical role of T-lymphocyte-derived MPs (TLMPs) is poorly understood. In the present study we focused on the ability of TLMP to promote OX40L-mediated Th2 responses. Purified human naïve or memory CD4+ T cells were stimulated with recombinant OX40L or TSLP-treated DCs (TSLP-DCs) in the presence of TLMP, and cytokine production by the primed T cells was examined. Although most TLMPs contain phosphatidylserine, only a few express lymphocyte functional antigen-1. TLMP remarkably enhanced TSLP-DC-driven or OX40L-driven Th2 responses from naïve T cells and the Th2 functional attributes of CRT+ CD4+ Th2 memory cells by the increased production of interleukin (IL)-5, IL-9 and IL-13. TLMP functions as a positive regulator of the TSLP-DC-OX40L axis that initiates and maintains Th2 cell-mediated inflammatory responses, and therefore, it might be a new therapeutic target for the treatment of allergic disorders.
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