AI Article Synopsis

  • The chemokine receptor CXCR3 is crucial for immune cell activation and migration, binding ligands CXCL9, CXCL10, and CXCL11, each with unique expression patterns and signaling effects.
  • CXCL9 and CXCL10 are pro-inflammatory during viral infections, while CXCL11 may cause immune tolerance, but its role is not fully understood due to genetic mutations in standard lab mice.
  • This study successfully used CRISPR/Cas9 to correct these mutations in C57BL/6 mice, allowing for the expression of CXCL11, and demonstrated that its presence does not affect acute antiviral responses, providing a new research tool for future studies of CXCL11.

Article Abstract

The chemokine receptor CXCR3 is expressed on immune cells to co-ordinate lymphocyte activation and migration. CXCR3 binds three chemokine ligands, CXCL9, CXCL10 and CXCL11. These ligands display distinct expression patterns and ligand signaling biases; however, how each ligand functions individually and collaboratively is incompletely understood. CXCL9 and CXCL10 are considered pro-inflammatory chemokines during viral infection, while CXCL11 may induce a tolerizing state. The investigation of the individual role of CXCL11 in vivo has been hampered as C57BL/6 mice carry several mutations that result in a null allele. Here, CRISPR/Cas9 was used to correct these mutations on a C57BL/6 background. It was validated that CXCL11 mice expressed CXCL11 protein in dendritic cells, spleen and lung. CXCL11 mice were largely phenotypically indistinguishable from C57BL/6 mice, both at steady-state and during two models of viral infection. While CXCL11 expression did not modify acute antiviral responses, this study provides a new tool to understand the role of CXCL11 in other experimental settings.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9542850PMC
http://dx.doi.org/10.1111/imcb.12541DOI Listing

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