Abstract

Researchers use Functional Imaging to Elucidate the Role of Cellular Zn²⁺ in Human Immunity

Article on Nature Immunology journal

An international consortium of researchers has found a new mutation in a gene harboring a reticulum-to-cytoplasm zinc transporter. The gene is called ZIP7 and it is responsible for the early onset of infections in patients.

These findings led them to uncover the role of ZIP7 in B cell development. To elucidate the cellular function of ZIP7, researchers used CRISPR-Cas9 mutagenesis to recreate the observed mutations in mice. They then studied primary cells with functional imaging and zinc biosensors to corroborate the mutations and see how cells handle zinc.

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Because of the intrinsic variability found in primary cells, the researchers had to rely on fluorescence lifetime imaging to probe the Zn2+ function in these cells. The observed ZIP7 mutations eliminated the natural Zn2+ gradient present in precursor B cells. The absence of this gradient is key for development of the immunodeficiency found in patients.

Tile scan on SP8 FALCON showing primary murine pre B cells expressing the eCALWY-6 Zn2+ (2+ in superscript) biosensor (cyan fluorescence) and the corresponding DIC images.
Tile scan on SP8 FALCON showing primary murine pre B cells expressing the eCALWY-6 Zn2+ (2+ in superscript) biosensor (cyan fluorescence) and the corresponding DIC images.

Read full article: https://www.nature.com/articles/s41590-018-0295-8

Consuelo Anzilotti et al:
An essential role for the Zn2+ transporter ZIP7 in B cell development

Nature Immunology volume 20, pages 350–361 (2019) 

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