Properdin and factor H production by human dendritic cells modulates their T‐cell stimulatory capacity and is regulated by IFN‐γ

Abstract

Dendritic cells (DCs) and complement are both key members of the innate and adaptive immune response. Recent experimental mouse models have shown that production of alternative pathway (AP) components by DCs strongly affects their ability to activate and regulate T‐cell responses. In this study we investigated the production and regulation of properdin (fP) and factor H (fH) both integral regulators of the AP, by DCs and tolerogenic DCs (tolDCs). Both fP and fH were produced by DCs, with significantly higher levels of both AP components produced by tolDCs. Upon activation with IFN‐γ both cells increased fH production, while simultaneously decreasing production of fP. IL‐27, a member of the IL‐12 family, increased fH, but production of fP remained unaffected. The functional capacity of fP and fH produced by DCs and tolDCs was confirmed by their ability to bind C3b. Inhibition of fH production by DCs resulted in a greater ability to induce allogenic CD4+ T‐cell proliferation. In contrast, inhibition of fP production led to a significantly reduced allostimulatory capacity. In summary, this study shows that production of fP and fH by DCs, differentially regulates their immunogenicity, and that the local cytokine environment can profoundly affect the production of fP and fH.

Properdin binds independent of complement activation in an in vivo model of anti–glomerular basement membrane disease

“…Conversely, the levels increased in tandem with SAP, suggesting that systemic inflammation may affect the secretion of properdin to circulation from activated inflammatory cells. 25,35,36 It must be noted that the range of mouse properdin seemed high compared with concentrations in human serum. This may be due to the use of recombinant mouse properdin as a standard that may not have the same distribution of properdin isoforms as is found in vivo.…”

Complement as a regulator of adaptive immunity

“…In concordance with these observations, it was shown that IFNγ-activated DCs resulted in increased expression of cell surface factor H. Inhibition of factor H expression resulted in increased CD4+ T cell activation and proliferation. These findings suggest a role for factor H in the regulation of DC function and its modulation of T cell responses [ 32 ].…”

Human Properdin Opsonizes Nanoparticles and Triggers a Potent Pro-inflammatory Response by Macrophages without Involving Complement Activation

“…Furthermore, treatment of DCs with siRNA targeting properdin reduced the proliferation of allogenic T cells, and this effect was more pronounced when combined with IFN-γ stimulation. Interestingly, IFN-γ reduced the production of properdin and factor H in both types of DCs ( 29 ). This demonstrates that local production of properdin is crucial for the DC and T cell responses.…”