Properdin produced by dendritic cells contributes to the activation of T cells

Essen, M.F. van; Schlagwein, N.; Gijlswijk-Janssen, D.J. van; Ruben, J.M.; Kooten, C. van; COMBAT Consortium

doi:doi:10.1016/j.imbio.2022.152246

The complement system does not only play an important role in the defence against microorganism and pathogens, but also contributes to the regulation of innate and adaptive immunity. Especially activation fragments C3a and C5a and complement activation at the interface of antigen presenting cell (APC) and T cell, were shown to have a role in T cell activation and proliferation. Whereas most complement factors are produced by the liver, properdin, a positive regulator of the C3 convertase, is mainly produced by myeloid cells. Here we show that properdin can be detected in myeloid cell infiltrate during human renal allograft rejection. In vitro, properdin is produced and secreted by human immature dendritic cells (iDCs), which is further increased by CD40-L-matured DCs (mDCs). Transfection with a specific properdin siRNA reduced properdin secretion by iDCs and mDCs, without affecting the expression of co-stimulatory markers CD80 and CD86. Co-culture of properdin siRNA-transfected iDCs...Show moreThe complement system does not only play an important role in the defence against microorganism and pathogens, but also contributes to the regulation of innate and adaptive immunity. Especially activation fragments C3a and C5a and complement activation at the interface of antigen presenting cell (APC) and T cell, were shown to have a role in T cell activation and proliferation. Whereas most complement factors are produced by the liver, properdin, a positive regulator of the C3 convertase, is mainly produced by myeloid cells. Here we show that properdin can be detected in myeloid cell infiltrate during human renal allograft rejection. In vitro, properdin is produced and secreted by human immature dendritic cells (iDCs), which is further increased by CD40-L-matured DCs (mDCs). Transfection with a specific properdin siRNA reduced properdin secretion by iDCs and mDCs, without affecting the expression of co-stimulatory markers CD80 and CD86. Co-culture of properdin siRNA-transfected iDCs and mDCs with human allogeneic T cells resulted in reduced T cell proliferation, especially under lower DC-T cell ratio's (1:30 and 1:90 ratio). In addition, T cell cytokines were altered, including a reduced TNF-alpha and IL-17 secretion by T cells co-cultured with properdin siRNA-transfected iDCs. Taken together, these results indicate a local role for properdin during the interaction of DCs and allogeneic T cells, contributing to the shaping of T cell proliferation and activation.Show less

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Properdin produced by dendritic cells contributes to the activation of T cells