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Cutting Edge: Genetic Characterization of IFN-Producing Killer Dendritic Cells¹

Fanny Guimont-Desrochers^*, Zachary John Cappello, Miguel Chagnon, Marcia McDuffie^, and Sylvie Lesage^2,*

^* Department of Microbiology and Immunology, University of Montreal and Maisonneuve-Rosemont Hospital Research Center, Montreal, Canada; Department of Microbiology and Department of Medicine, University of Virginia, Charlottesville, VA 22908; and Department of Mathematics and Statistics, University of Montreal, Montreal, Canada

The combined phenotypic expression of CD11c^lowB220⁺CD122⁺DX5⁺ has been used to define a novel cell type termed IFN-producing killer dendritic cells (IKDC). IKDC readily produce IFN- and demonstrate spontaneous cytotoxic activity toward tumors, suggesting that a modulation of IKDC number may be beneficial in cancer treatment. We examined various mouse strains and found that IKDC number was highly variable between the different strains. A linkage analysis associated the distal arm of chromosome 7 with variations in IKDC number. The genetic contribution of chromosome 7 to the regulation of IKDC number was confirmed through the use of congenic mice. We further demonstrate that IKDC proportion is regulated by intrinsic hematopoietic factors. We discuss the role of various candidate genes in the regulation of this newly described cell type and its implication in therapy.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This project was supported by Diabète Québec and La Fondation de l’Hôpital Maisonneuve-Rosemont. S.L. is a recipient of a Junior 1 scholarship from Fonds de la recherche en santé du Québec. F.G.-D. is a recipient of scholarships from La Fondation du Dr. Georges Phénix, Diabète Québec, and the University of Montreal.

² Address correspondence and reprint requests to Dr. Sylvie Lesage, Hôpital Maisonneuve-Rosemont, Centre de Recherche, 5415 Boulevard de l’Assomption, Montréal, Québec H1T 2M4, Canada. E-mail address: sylvie.lesage{at}umontreal.ca

³ Abbreviations used in this paper: DC, dendritic cell; pDC, plasmacytoid DC; IKDC, interferon-producing killer DC; NOD, nonobese diabetic.

⁴ The online version of this article contains supplemental material.