Ap4A Regulates Directional Mobility and Antigen Presentation in Dendritic Cells

Shin La Shu; Lakshmi Bhargavi Paruchuru; Neil Quanwei Tay; Yen Leong Chua; Adeline Shen Yun Foo; Chris Maolin Yang; Ka Hang Liong; Esther Geok Liang Koh; Angeline Lee; Hovav Nechushtan; Ehud Razin; David Michael Kemeny

doi:10.1016/j.isci.2019.05.045

Ap₄A Regulates Directional Mobility and Antigen Presentation in Dendritic Cells

iScience. 2019 Jun 28:16:524-534. doi: 10.1016/j.isci.2019.05.045. Epub 2019 Jun 4.

Affiliations

¹ Immunology Programme, Department of Microbiology, Centre for Life Sciences, National University of Singapore, #03-09, 28 Medical Drive, Singapore 117456, Singapore; NUS-HUJ-CREATE, 1 Create Way, Innovation Wing #03-09, Singapore 138602, Singapore.
² Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada, Hebrew University of Jerusalem, Jerusalem 91120, Israel.
³ Immunology Programme, Department of Microbiology, Centre for Life Sciences, National University of Singapore, #03-09, 28 Medical Drive, Singapore 117456, Singapore.
⁴ NUS-HUJ-CREATE, 1 Create Way, Innovation Wing #03-09, Singapore 138602, Singapore.
⁵ Sharett Institute of Oncology, Hadassah Hebrew University Medical Center, Hebrew University of Jerusalem, POB 12000 Jerusalem, Israel. Electronic address: hovavnech@hadassah.org.il.
⁶ NUS-HUJ-CREATE, 1 Create Way, Innovation Wing #03-09, Singapore 138602, Singapore; Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada, Hebrew University of Jerusalem, Jerusalem 91120, Israel. Electronic address: ehudr@ekmd.huji.ac.il.
⁷ Immunology Programme, Department of Microbiology, Centre for Life Sciences, National University of Singapore, #03-09, 28 Medical Drive, Singapore 117456, Singapore; NUS-HUJ-CREATE, 1 Create Way, Innovation Wing #03-09, Singapore 138602, Singapore. Electronic address: mickdm@nus.edu.sg.

Abstract

The significance of intracellular Ap₄A levels over immune activity of dendritic cells (DCs) has been studied in Nudt2^fl/fl/CD11c-cre mice. The transgenic mice have been generated by crossing floxed NUDT2 gene mice with DC marker CD11c recombinase (cre) mice. The DCs derived from these mice have higher levels of Ap₄A (≈30-fold) compared with those derived from Nudt2^+/+ mice. Interestingly, the elevated Ap₄A in DCs has led them to possess higher motility and lower directional variability. In addition, the DCs are able to enhance immune protection indicated by the higher cross-presentation of antigen and priming of CD8⁺ OT-I T cells. Overall, the study denotes prominent impact of Ap₄A over the functionality of DCs. The Nudt2^fl/fl/CD11c-cre mice could serve as a useful tool to study the influence of Ap₄A in the critical immune mechanisms of DCs.

Keywords: Immune Response; Immunology; Model Organism; Molecular Mechanism of Behavior.