Journal
NATURE IMMUNOLOGY
Volume 17, Issue 10, Pages 1167-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3535
Keywords
-
Categories
Funding
- National Key Basic Research Program of China [2013CB530502, 2014CB542101]
- National Natural Science Foundation of China [81522019, 31390431, 31270966, 81471567]
- Shanghai Pujiang Program [14PJ1410800]
Ask authors/readers for more resources
CD8 alpha(+) dendritic cells (DCs) are specialized at cross-presenting extracellular antigens on major histocompatibility complex (MHC) class I molecules to initiate cytotoxic T lymphocyte (CTL) responses; however, details of the mechanisms that regulate cross-presentation remain unknown. We found lower expression of the lectin family member Siglec-G in CD8 alpha(+) DCs, and Siglec-G deficient (Siglecg(-/-)) mice generated more antigen-specific CTLs to inhibit intracellular bacterial infection and tumor growth. MHC class I-peptide complexes were more abundant on Siglecg(-/-) CD8 alpha(+) DCs than on Siglecg(+/+) CD8 alpha(+) DCs. Mechanistically, phagosome-expressed Siglec-G recruited the phosphatase SHP-1, which dephosphorylated the NADPH oxidase component p47(phox) and inhibited the activation of NOX2 on phagosomes. This resulted in excessive hydrolysis of exogenous antigens, which led to diminished formation of MHC class I-peptide complexes for cross-presentation. Therefore, Siglec-G inhibited DC cross-presentation by impairing such complex formation, and our results add insight into the regulation of cross-presentation in adaptive immunity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available