Secretory leukocyte proteinase inhibitor-competent DNA deposits are potent stimulators of plasmacytoid dendritic cells: implication for psoriasis.
Secretory leukocyte proteinase inhibitor (SLPI) is a well-established inhibitor of serine proteases such as human neutrophil elastase (HNE) and a NF-κB regulatory agent in immune cells. In this paper, we report that SLPI plays a previously uncharacterized role in regulating activation of plasmacytoid dendritic cells (pDCs). As the main source of IFN type I (IFNI), pDCs are crucial contributors to inflammatory and likely wound-healing responses associated with psoriasis. The mechanisms responsible for activation of pDCs in psoriatic skin are therefore of substantial interest. We demonstrate that in lesional skin of psoriasis patients, SLPI together with its enzymatic target HNE and DNA, is a component of neutrophil extracellular traps (NETs). Whereas SLPI(+) neutrophils and NETs were found to colocalize with pDCs in psoriatic skin, a mixture of SLPI with neutrophil DNA and HNE induced a marked production of IFNI by pDCs. IFNI synthesis by stimulated pDCs was dependent on intracellular DNA receptor TLR9. Thus, SLPI may contribute to psoriasis by enabling pDCs to sense extracellular DNA and produce IFNI.
Department of Immunology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, 30-387 Kraków, Poland.
Joanna
J
Skrzeczynska-Moncznik
Agnieszka
A
Wlodarczyk
Katarzyna
K
Zabieglo
Monika
M
Kapinska-Mrowiecka
Ewa
E
Marewicz
Adam
A
Dubin
Jan
J
Potempa
Joanna
J
Cichy
D000328:Adult; D004247:DNA / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007370:Interferon Type I / Q000276:immunology; D019272:Leukocyte Elastase / Q000276:immunology; D008297:Male; D011565:Psoriasis / Q000276:immunology*; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000276:immunology*
D007370:Interferon Type I; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D004247:DNA; D019272:Leukocyte Elastase