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

Yifan Zhan; Emma M Carrington; Annemarie van Nieuwenhuijze; Sammy Bedoui; Shirley Seah; Yuekang Xu; Nancy Wang; Justine D Mintern; Jose A Villadangos; Ian P Wicks; Andrew M Lew

doi:10.1002/eji.201141540

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

Eur J Immunol. 2011 Sep;41(9):2585-95. doi: 10.1002/eji.201141540. Epub 2011 Aug 4.

Authors

Yifan Zhan¹, Emma M Carrington, Annemarie van Nieuwenhuijze, Sammy Bedoui, Shirley Seah, Yuekang Xu, Nancy Wang, Justine D Mintern, Jose A Villadangos, Ian P Wicks, Andrew M Lew

Affiliation

¹ Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia. [email protected]

PMID: 21660938
DOI: 10.1002/eji.201141540

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, Bacterial / immunology
Antigens, CD / genetics
Antigens, CD / immunology
Antigens, CD / metabolism*
CD8 Antigens / biosynthesis
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
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*
Immunomodulation
Integrin alpha Chains / genetics
Integrin alpha Chains / immunology
Integrin alpha Chains / metabolism*
Listeria monocytogenes / immunology*
Listeria monocytogenes / pathogenicity
Listeriosis / immunology*
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Spleen / pathology

Substances

Antigens, Bacterial
Antigens, CD
CD8 Antigens
Integrin alpha Chains
alpha E integrins
Granulocyte-Macrophage Colony-Stimulating Factor