Cutting Edge: PDGF-DD Binding to NKp44 Costimulates TLR9 Signaling and Proinflammatory Cytokine Secretion in Human Plasmacytoid Dendritic Cells

Alexander David Barrow, Marina Cella, Melissa Anne Edeling, Md Abdullah Al Kamran Khan, Luisa Cervantes-Barraga, Mattia Bugatti, Christian Schmedt, William Vermi, Marco Colonna

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

NKp44 is a human receptor originally found on activated NK cells, group 1 and group 3 innate lymphoid cells that binds dimers of platelet-derived growth factor D (PDGFDD). NKp44 is also expressed on tissue plasmacytoid dendritic cells (PDCs), but NKp44-PDGF-DD interaction on PDCs remains unstudied. Engagement of NKp44 with PDGF-DDin vitro enhanced PDC secretion of IFN-a, TNF, and IL-6 in response to the TLR9 ligand CpGODN, but not TLR7/8 ligands. In tissues, PDCs were found in close contact with PDGF-DD-expressing cells in the high endothelial venules and epithelium of tonsils, melanomas, and skin lesions infected with Molluscum contagiosum. Recombinant PDGF-DD enhanced the serum IFN-a response to systemic HSV-1 infection in a humanizedmousemodel.We conclude thatNKp44 integrates with TLR9 signaling to enhance PDC cytokine production. These findings may have bearings for immune responses to TLR9-based adjuvants, therapy for tumors expressing PDGF-DD, and infections with DNA viruses that induce PDGF-DD expression to enhance viral spread.

Original languageEnglish
Pages (from-to)369-374
Number of pages6
JournalJournal of Immunology
Volume212
Issue number3
DOIs
StatePublished - Feb 1 2024

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