Serpinb9 is a marker of antigen cross-presenting dendritic cells

M S Mangan; J Vega-Ramos; L T Joeckel; A J Mitchell; A Rizzitelli; B Roediger; D Kaiserman; W W Weninger; J A Villadangos; P I Bird

doi:10.1016/j.molimm.2016.12.011

Serpinb9 is a marker of antigen cross-presenting dendritic cells

Mol Immunol. 2017 Feb:82:50-56. doi: 10.1016/j.molimm.2016.12.011. Epub 2016 Dec 24.

Authors

M S Mangan¹, J Vega-Ramos², L T Joeckel¹, A J Mitchell³, A Rizzitelli¹, B Roediger³, D Kaiserman¹, W W Weninger⁴, J A Villadangos⁵, P I Bird⁶

Affiliations

¹ Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, 3800, Australia.
² Department of Microbiology and Immunology, Doherty Institute of Infection and Immunity, University of Melbourne, Parkville, Victoria 3010, Australia.
³ The Centenary Institute, Royal Prince Alfred Hospital, Sydney, New South Wales, 2000, Australia.
⁴ The Centenary Institute, Royal Prince Alfred Hospital, Sydney, New South Wales, 2000, Australia; Discipline of Dermatology, University of Sydney, New South Wales, 2006, Australia.
⁵ Department of Microbiology and Immunology, Doherty Institute of Infection and Immunity, University of Melbourne, Parkville, Victoria 3010, Australia; Department of Biochemistry and Molecular Biology, Bio21 Institute, University of Melbourne, Victoria, 3010, Australia.
⁶ Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, 3800, Australia. Electronic address: phil.bird@monash.edu.

PMID: 28024184
DOI: 10.1016/j.molimm.2016.12.011

Abstract

Serpinb9 (Sb9, also called Spi6) is an intracellular inhibitor of granzyme B (grB) that protects cytotoxic lymphocytes from grB-mediated death. In addition, Sb9 is also expressed in accessory immune cells, including dendritic cells (DCs), although its role is debated. Recently, we have demonstrated that Sb9 plays a grB-independent role in cross-presentation of antigens by CD8⁺ DCs. Here, using a mouse line expressing green fluorescent protein knocked in under the control of the Sb9 promoter, we demonstrate that Sb9 expression is highest in those tissue-resident and migratory DC subsets capable of cross-presentation. Further, we show that CD8⁺ DCs can be divided into two subsets based on Sb9 expression, and that only the subset expressing higher levels of Sb9 is capable of cross-presentation. These findings add support for role for Sb9 cross-presentation, and indicate that high Sb9 expression is a novel marker of cross-presentation capable DCs.

Keywords: Cross-presentation; DCs; Dendritic cell; Granzyme B; SPI6; Serpinb9.

Publication types

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

MeSH terms

Animals
Cross-Priming / immunology*
Dendritic Cells / immunology*
Female
Flow Cytometry
Gene Knock-In Techniques
Male
Membrane Proteins / immunology*
Mice
Mice, Inbred C57BL
Serpins / immunology*

Substances

Membrane Proteins
Serpins
Serpinb9 protein, mouse