Inhibition of CXCR1 and CXCR2 attenuates the recruitment of allergic inflammatory cells to the lungs
Neutrophils express CXCR1 and CXCR244-46. Based on our observations showing the remarkable efficacy of ladarixin in blocking CDE-challenge-induced recruitment of inflammatory cells (Fig 2-4) , we hypothesized that various inflammatory cells recruited by CDE challenge also express CXCR1 and CXCR2. To test this hypothesis, we quantified the number of CXCR1 and CXCR2 expressing inflammatory cells in the lung in CDE-MCM that secrete cytokines or expression key transcription factors. CDE challenge in mice subjected to CDE-MCM increased the recruitment of CXCR1-expressing (Fig 5A ) and CXCR2-expressing (Fig 5B ) GATA3-, IL4-, IL5-, IL13-, RORγt-, and IL17-expressing T-cells. Furthermore, CDE challenge increased the recruitment of CXCR1-expressing (Fig 5A ) and CXCR2-expressing (Fig 5B ) neutrophils, eosinophils, IL23-expressing neutrophils, and IL23-expressing eosinophils. Oral administration of ladarixin blocked CDE challenge-induced recruitment of CXCR1-expressing (Fig 5A ) and CXCR2-expressing (Fig 5B ) GATA3-, IL4-, IL5-, IL13-, RORγt-, and IL17-expressing T-cells, neutrophils, eosinophils, IL23-expressing neutrophils, and IL23-expressing eosinophils. Together these results indicate that CXCR1 and CXCR2 are key regulators of Th2 and Th17-mediated allergic inflammation.