The mouse dendritic cell marker CD11c is down-regulated upon cell activation through Toll-like receptor triggering

• Published in: Immunobiology (1979) 2013-01, Vol.218 (1), p.28-39
• Main Authors: Singh-Jasuja, Harpreet, Thiolat, Allan, Ribon, Matthieu, Boissier, Marie-Christophe, Bessis, Natacha, Rammensee, Hans-Georg, Decker, Patrice
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Allergy and Immunology; Animals; Antigen-presenting cells; Biomarkers - metabolism; Bone marrow; CD11c antigen; CD11c Antigen - genetics; CD11c Antigen - metabolism; CD11c expression; CD40 antigen; CD40 Antigens - genetics; CD40 Antigens - metabolism; CD86 antigen; Cell activation; Cell Differentiation - drug effects; Cell Differentiation - immunology; Cell surface; Cells, Cultured; Cytokines; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Down-Regulation - drug effects; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - metabolism; Humans; Lipopolysaccharides; Major histocompatibility complex; Mice; Mice, Inbred C57BL; Mice, Knockout; Mixed leukocyte reaction; MyD88; MyD88 protein; Myeloid Differentiation Factor 88 - genetics; Myeloid Differentiation Factor 88 - metabolism; Signal Transduction - genetics; Signal Transduction - immunology; Spleen; TLR3 protein; Toll-like receptor agonists; Toll-like receptors; Toll-Like Receptors - agonists; Toll-Like Receptors - immunology
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/j.imbio.2012.01.021

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.