GM‐CSF increases cross‐presentation and CD103 expression by mouse CD8+ spleen dendritic cells

• Published in: European journal of immunology 2011-09, Vol.41 (9), p.2585-2595
• Main Authors: Zhan, Yifan, Carrington, Emma M., van Nieuwenhuijze, Annemarie, Bedoui, Sammy, Seah, Shirley, Xu, Yuekang, Wang, Nancy, Mintern, Justine D., Villadangos, Jose A., Wicks, Ian P., Lew, Andrew M.
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Bacterial - immunology; Antigens, CD - genetics; Antigens, CD - immunology; Antigens, CD - metabolism; CD103; CD8 Antigens - biosynthesis; CD8+ DC; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - microbiology; CD8-Positive T-Lymphocytes - pathology; Cells, Cultured; Cross-Priming - genetics; Cross‐presentation; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - microbiology; Dendritic Cells - pathology; Gene Expression Regulation - genetics; Granulocyte-Macrophage Colony-Stimulating Factor - genetics; Granulocyte-Macrophage Colony-Stimulating Factor - immunology; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Granulocyte‐macrophage colony‐stimulating factor; Immunomodulation; Integrin alpha Chains - genetics; Integrin alpha Chains - immunology; Integrin alpha Chains - metabolism; Listeria monocytogenes; Listeria monocytogenes - immunology; Listeria monocytogenes - pathogenicity; Listeriosis - immunology; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Spleen; Spleen - pathology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201141540

Resident CD8+ DCs perform several functions, including cross‐presenting antigen and rapidly engulfing the Gram‐positive intracellular pathogen Listeria monocytogenes. Little is known about how these functions of CD8+ DCs are modulated. Here, we show that granulocyte‐macrophage CSF (GM‐CSF), a cytokine that exists at low levels at steady state but is elevated during infection and inflammation, enhances cross‐presentation and rapid uptake of L. monocytogenes by resident CD8+ DCs. This previously unrecognized functional enhancement of CD8+ DCs by GM‐CSF was independent of promoting DC survival in vitro. Enhancement of these functions by GM‐CSF was also marked by CD103 expression on CD8+ DCs that was strongly regulated by GM‐CSF. Our findings not only identify GM‐CSF as a key molecule regulating CD8+ DC function, but also as a factor responsible for functional heterogeneity of CD8+ DCs that is at least substantially demarcated by CD103 expression.