Human XCR1+ dendritic cells derived in vitro from CD34 + progenitors closely resemble blood dendritic cells, including their adjuvant responsiveness, contrary to monocyte-derived dendritic cells

Sreekumar Balan, Vincent Ollion, Nicholas Colletti, Rabie Chelbi, Frédéric Montanana-Sanchis, Hong Liu, Thien Phong Vu Manh, Cindy Sanchez, Juliette Savoret, Ivan Perrot, Anne Claire Doffin, Even Fossum, Didier Bechlian, Christian Chabannon, Bjarne Bogen, Carine Asselin-Paturel, Michael Shaw, Timothy Soos, Christophe Caux, Jenny Valladeau-GuilemondMarc Dalod

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

Abstract

Human monocyte-derived dendritic cell (MoDC) have been used in the clinic with moderately encouraging results. Mouse XCR1+ DC excel at cross-presentation, can be targeted in vivo to induce protective immunity, and share characteristics with XCR1+ human DC. Assessment of the immunoactivation potential of XCR1+ human DC is hindered by their paucity in vivo and by their lack of a well-defined in vitro counterpart. We report in this study a protocol generating both XCR1+ and XCR1- human DC in CD34+ progenitor cultures (CD34-DC). Gene expression profiling, phenotypic characterization, and functional studies demonstrated that XCR12 CD34-DC are similar to canonical MoDC, whereas XCR1+ CD34-DC resemble XCR1+ blood DC (bDC). XCR1+ DC were strongly activated by polyinosinic-polycytidylic acid but not LPS, and conversely for MoDC. XCR1+ DC and MoDC expressed strikingly different patterns of molecules involved in inflammation and in cross-talk with NK or T cells. XCR1+ CD34-DC but not MoDC efficiently cross-presented a cell-associated Ag upon stimulation by polyinosinic-polycytidylic acid or R848, likewise to what was reported for XCR1+ bDC. Hence, it is feasible to generate high numbers of bona fide XCR1+ human DC in vitro as a model to decipher the functions of XCR1+ bDC and as a potential source of XCR1+ DC for clinical use.

Original languageEnglish
Pages (from-to)1622-1635
Number of pages14
JournalJournal of Immunology
Volume193
Issue number4
DOIs
StatePublished - 15 Aug 2014
Externally publishedYes

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