The Soluble Cytoplasmic Tail of CD45 (ct-CD45) Regulates Dendritic Cell Activation and Function via TLR4 Signaling

The soluble cytoplasmic tail of the prototypic receptor-like protein tyrosine phosphatase (PTP) CD45 (ct-CD45) is cleaved and released into the human plasma by activated phagocytes. Released ct-CD45 was found to inhibit T cell proliferation and cytokine production via engagement of Toll-like receptor 4 (TLR4). In this study, we analyzed the impact of the ct-CD45/TLR4 pathway on the function of human monocyte-derived dendritic cells (DCs). We could demonstrate that activation of DCs by ct-CD45 upregulated the expression of certain cell surface markers (e.g., CD71 and CD86) and induced IL-10 production via TLR4. Yet, in contrast to stimulation with LPS, other typical cell surface markers and cytokines were not upregulated or induced in DCs by ct-CD45. The T cell proliferation-stimulatory capacity of DCs was not modulated by ct-CD45 treatment. However, treatment of DCs with ct-CD45 modulated the cytokine profile in co-cultured T cells. While IFN-γ production induced by DCs was strongly inhibited, the release of IL-4 was increased in T cells upon stimulation with ct-CD45-treated DCs. In contrast, ct-CD45-stimulated DCs induced IL-2 and IL-10 production in co-cultured T cells comparable to untreated DCs. In summary, we could demonstrate that ct-CD45 acts as an immunoregulatory factor for DCs via a non-canonical TLR4-dependent activation pathway.