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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. 2014
Sreekumar Balan, and
Vincent Ollion, and
Nicholas Colletti, and
Rabie Chelbi, and
Frédéric Montanana-Sanchis, and
Hong Liu, and
Thien-Phong Vu Manh, and
Cindy Sanchez, and
Juliette Savoret, and
Ivan Perrot, and
Anne-Claire Doffin, and
Even Fossum, and
Didier Bechlian, and
Christian Chabannon, and
Bjarne Bogen, and
Carine Asselin-Paturel, and
Michael Shaw, and
Timothy Soos, and
Christophe Caux, and
Jenny Valladeau-Guilemond, and
Marc Dalod
Centre d'Immunologie de Marseille-Luminy, UNIV UM2, Aix-Marseille Université, Parc Scientifique et Technologique de Luminy, 13288 Marseille, France; INSERM, Unité Mixte de Recherche 1104, 13288 Marseille, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7280, 13288 Marseille, France;
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 XCR1(-) 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.
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