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Updated: May 30, 2026
Advanced Imaging of Lung Homing Human Lymphocytes in an Experimental In Vivo Model of Allergic Inflammation Based on Light-sheet Microscopy
Published on: April 16, 2019
Targeting CXCR3 reduces ligand-induced T-cell activation but not development of lung allergic responses
Yoo Seob Shin1, Katsuyuki Takeda, Hiroshi Ohnishi
1Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, Colorado 80206, USA.
Background:
Asthma is a chronic airway inflammatory disease that is associated with a large influx of inflammatory cells. Several chemokines and chemokine receptors play critical roles in the development of allergic airway inflammation.
Objective:
Because polarized human T(H)2 cells express a functional CXCR3 chemokine receptor, we evaluated the effects of a selective CXCR3 inhibitor in a mouse model of allergic airway disease.
Methods:
Ovalbumin-specific CD8(+) T effector cells were generated from OT-1 mice in the presence of interleukin 2. The activity of a CXCR3 inhibitor was examined in vitro by monitoring Ca(2+) influx after receptor ligation. In vivo, the activity was assessed in sensitized and challenged mice by monitoring airway function, inflammatory parameters, including cellular infiltrates and cytokines in the bronchoalveolar lavage fluid.
Results:
Approximately 40% of CD8(+) T effector cells expressed the CXCR3 receptor. In vitro, CXCR3 antagonism reduced Ca(2+) influx after receptor engagement. In contrast, the CXCR3 antagonist had little to no effect on airway function or inflammatory parameters despite adequate exposure levels.
Conclusions:
CXCR3 antagonism did not prevent allergen-induced airway hyperresponsiveness or airway inflammation in a mouse allergy model despite having activity in in vitro functional assays.
