Prof. Xuetao Cao’s group reported the regulatory mechanism of Siglec-G to DC cross-presentation
Source：Yuanyuan Ding
2016-12-02
Recently, Prof. Xuetao Cao (Academician of Chinese Academy of Engineering, Director of Chinese Academy of Medical Sciences) and Dr. Yuanyuan Ding, Dr. Yiqi Liu (Zhejiang University, School of Medicine) and Prof. ZhenhongGuo (National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University) has published a paper in Nature Immunology about the function and mechanisms of a member of lectin, Siglec-G inhibits cross-presentation of DCs (Ding Y. et al, The lectinSiglec-G inhibits dendritic cell cross-presentation by impairing MHC class I-peptide complex formation.Nat Immunol. 2016 Oct;17(10):1167-75.)
The presentation of exogenous antigens via MHC class I molecules to initiate cytotoxic CD8+ CTL responses is known as ‘cross-presentation’ and is an essential process for immunological defense against viruses, intracellular bacteria and tumors. DCs perform important functions to initiate adaptive immune responses, and splenic CD8α+ DCs are considered to be the most potent at cross-presentation, but thedetails of the mechanisms underlying the differences of DC subsets and their ability to cross-present remain unclear.
In this paper, Prof. Cao’s team found lower expression of the lectin family member Siglec-G in CD8+ 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−/−CD8α+ DCs than on Siglecg+/+CD8α+ DCs. Mechanistically, phagosome-expressed Siglec-G recruited the phosphatase SHP-1, which dephosphorylated the NADPH oxidase component p47phox 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.
The results add insight into the regulation of cross-presentation in adaptive immunity, provide new mechanistic insight into the differences among splenic DC subsets in their cross-presentation. It also broaden knowledge of the regulatory functions of lectins in adaptive immune responses.
The presentation of exogenous antigens via MHC class I molecules to initiate cytotoxic CD8+ CTL responses is known as ‘cross-presentation’ and is an essential process for immunological defense against viruses, intracellular bacteria and tumors. DCs perform important functions to initiate adaptive immune responses, and splenic CD8α+ DCs are considered to be the most potent at cross-presentation, but thedetails of the mechanisms underlying the differences of DC subsets and their ability to cross-present remain unclear.
In this paper, Prof. Cao’s team found lower expression of the lectin family member Siglec-G in CD8+ 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−/−CD8α+ DCs than on Siglecg+/+CD8α+ DCs. Mechanistically, phagosome-expressed Siglec-G recruited the phosphatase SHP-1, which dephosphorylated the NADPH oxidase component p47phox 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.
The results add insight into the regulation of cross-presentation in adaptive immunity, provide new mechanistic insight into the differences among splenic DC subsets in their cross-presentation. It also broaden knowledge of the regulatory functions of lectins in adaptive immune responses.
