title: The mouse dendritic cell marker CD11c is down-regulated upon cell activation through Toll-like receptor triggering.
abstract: Dendritic cells (DC) play a key role in regulating immune responses and are the best professional antigen-presenting cells. Two major DC populations are defined in part according to cell surface CD11c expression levels. Unexpectedly, we observed that mouse DC strongly down-regulate the typical DC marker CD11c upon activation. To better characterize DC responses, we have analyzed CD11c expression on mouse and human myeloid DC after Toll-like receptor (TLR) triggering. Here we show that mouse bone marrow-derived DC (BMDC) as well as spleen DC down-regulate cell surface CD11c upon activation by TLR3/4/9 agonists. In all cases, full DC activation was reached, as determined by cytokine secretion, cell stimulation in mixed leukocyte reactions (MLR), and CD40/CD86/major histocompatibility complex (MHC) up-regulation. Interestingly, membrane CD11c down-regulation correlated with increased cytoplasmic pools of CD11c. In contrast to the up-regulation of CD40 and MHC class II molecules, lipopolysaccharide (LPS)-induced CD11c down-regulation was MyD88-dependent. Polyinosinic-polycytidylic acid (poly I:C), which does not signal through MyD88, also induced cell surface CD11c down-regulation. Notably, CD11c down-regulation was not observed upon activation of human DC, either through TLR-dependent or -independent cell activation. Thus, activated mouse DC may be transiently CD11c-negative in vivo, hampering the identification of those cells. On the other hand, cell surface CD11c down-regulation may serve as a new activation marker for mouse DC.
authors.affiliation: Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.
authors.forename: Harpreet
authors.initials: H
authors.lastname: Singh-Jasuja
authors.forename: Allan
authors.initials: A
authors.lastname: Thiolat
authors.forename: Matthieu
authors.initials: M
authors.lastname: Ribon
authors.forename: Marie-Christophe
authors.initials: MC
authors.lastname: Boissier
authors.forename: Natacha
authors.initials: N
authors.lastname: Bessis
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.forename: Patrice
authors.initials: P
authors.lastname: Decker
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D039521:CD11c Antigen / Q000235:genetics / Q000378:metabolism*; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D015536:Down-Regulation / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D051193:Toll-Like Receptors / Q000819:agonists / Q000276:immunology*
chemical_list: D015415:Biomarkers; D039521:CD11c Antigen; D019013:CD40 Antigens; D000949:Histocompatibility Antigens Class II; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors