PMID- 28105653 OWN - NLM STAT- MEDLINE DCOM- 20170718 LR - 20181113 IS - 1521-4141 (Electronic) IS - 0014-2980 (Print) IS - 0014-2980 (Linking) VI - 47 IP - 3 DP - 2017 Mar TI - Properdin and factor H production by human dendritic cells modulates their T-cell stimulatory capacity and is regulated by IFN-gamma. PG - 470-480 LID - 10.1002/eji.201646703 [doi] AB - 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-gamma 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. CI - (c) 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Dixon, Karen O AU - Dixon KO AD - Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands. AD - Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA. FAU - O'Flynn, Joseph AU - O'Flynn J AD - Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands. AD - Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Klar-Mohamad, Ngaisah AU - Klar-Mohamad N AD - Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands. FAU - Daha, Mohamed R AU - Daha MR AD - Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands. FAU - van Kooten, Cees AU - van Kooten C AD - Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Eur J Immunol JT - European journal of immunology JID - 1273201 RN - 0 (Interleukin-27) RN - 0 (Isoantigens) RN - 0 (RNA, Small Interfering) RN - 11016-39-0 (Properdin) RN - 80295-43-8 (Complement C3b) RN - 80295-65-4 (Complement Factor H) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - CD4-Positive T-Lymphocytes/*immunology MH - Cell Proliferation MH - Cells, Cultured MH - Complement C3b/metabolism MH - Complement Factor H/genetics/*metabolism MH - *Complement Pathway, Alternative MH - Dendritic Cells/*physiology MH - Humans MH - Immune Tolerance MH - Interferon-gamma/metabolism MH - Interleukin-27/metabolism MH - Isoantigens/immunology MH - Lymphocyte Activation MH - Properdin/genetics/*metabolism MH - RNA, Small Interfering/genetics PMC - PMC5363362 OTO - NOTNLM OT - Complement OT - Cytokines OT - Factor H OT - IFN-gamma OT - IL-27 OT - Properdin OT - Tolerogenic dendritic cells EDAT- 2017/01/21 06:00 MHDA- 2017/07/19 06:00 PMCR- 2017/03/23 CRDT- 2017/01/21 06:00 PHST- 2016/08/29 00:00 [received] PHST- 2016/12/16 00:00 [revised] PHST- 2017/01/17 00:00 [accepted] PHST- 2017/01/21 06:00 [pubmed] PHST- 2017/07/19 06:00 [medline] PHST- 2017/01/21 06:00 [entrez] PHST- 2017/03/23 00:00 [pmc-release] AID - EJI3845 [pii] AID - 10.1002/eji.201646703 [doi] PST - ppublish SO - Eur J Immunol. 2017 Mar;47(3):470-480. doi: 10.1002/eji.201646703.