CXCR4 antagonism corrects neutrophil abnormalities and reduces pneumonia severity in a pharmacological mouse model of CXCR2 loss-of-function-mediated neutropenia.

ABSTRACT:

Background

The CXCR4 and CXCR2 chemokine receptor axes play critical but opposing roles in regulating neutrophil retention and release from the bone marrow (BM). Gain-of-function (GOF) variants in CXCR4 are associated with WHIM syndrome, characterized by neutropenia, lymphopenia, frequent infections, warts, and myelokathexis. Similarly, loss-of-function (LOF) variants in CXCR2 also result in neutropenia, increased infection susceptibility and myelokathexis. Mavorixafor, an orally bioavailable CXCR4 antagonist, has shown meaningful increases in absolute neutrophil count and reduced infections in WHIM syndrome patients. However, it remains unclear whether CXCR4 antagonism can mitigate the pathogenic characteristics observed in individuals with CXCR2 LOF mutations.

Methods

This

SUBMITTER: Nguyen CH 

PROVIDER: S-EPMC12727938 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature