Different Polyubiquitinated Bodies in Human Dendritic Cells: IL-4 Causes PaCS during Differentiation while LPS or IFNα Induces DALIS during Maturation

Daniela Montagna, Patrizia Sommi, Vittorio Necchi, Agostina Vitali, Enrica Montini, Ilaria Turin, Daniela Ferraro, Vittorio Ricci, Enrico Solcia

Research output: Contribution to journalArticlepeer-review

Abstract

Two types of polyubiquitin-reactive cytoplasmic bodies, particulate cytoplasmic structures (PaCS) and dendritic cell (DC) aggresome-like induced structures (DALIS), were analyzed by electron microscopy, immunocytochemistry, immunoblotting, and flow cytometry in DC obtained from human blood monocytes incubated with GM-CSF plus IL-4 (IL4-DC), GM-CSF plus IFNα (IFN-DC), or GM-CSF alone (GM-DC), with or without LPS maturation. PaCS developed as monomorphic aggregates of proteasome-reactive barrel-like particles only in ribosomes-rich cytoplasmic areas of differentiating IL4-DC. In contrast, DALIS formed as vesicular bodies storing K63-linked ubiquitinated proteins by coalescence of increased endosomal structures, in IFN-DC or after LPS maturation of GM-DC. DALIS-forming cells showed incomplete morphological and functional DC-type differentiation when compared to PaCS-forming IL4-DC. PaCS and DALIS may have different function as well as different origin and cytochemistry. DALIS may be a transient accumulation site of potentially antigenic polyubiquitinated proteins during their processing and presentation. PaCS are found under physiologic or pathologic conditions associated with increased/deranged protein synthesis and increased ubiquitin-proteasome activity. Given its high heat-shock protein content PaCS may work as a quality control structure for newly synthesized, cytosolic proteins. This comparative analysis suggests that PaCS and DALIS have distinctive roles in DC.

Original languageEnglish
Article number1844
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

ASJC Scopus subject areas

  • General

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