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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
ICOS ligand expression is essential for allergic airway hyperresponsiveness
Kamran Kadkhoda1, Shuhe Wang, Yijun Fan
1Immune Regulation of Allergy Research Group, Laboratory for Infection and Immunity, Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0W3, Canada.
Inducible co-stimulator ligand (ICOSL) deficiency in mice significantly reduces allergic airway inflammation and hyperresponsiveness. This suggests ICOSL is crucial for developing asthma-like conditions by promoting T(h)2 responses and IgE production.
Area of Science:
- Immunology
- Allergy Research
- Respiratory Medicine
Background:
- Inducible co-stimulator ligand (ICOSL) is a co-stimulatory molecule vital for T-cell responses.
- T(h)2 immune responses are central to allergic conditions like asthma.
Purpose of the Study:
- To investigate the role of ICOSL in allergic airway inflammation and hyperresponsiveness.
- To elucidate ICOSL's impact on immune responses in a mouse model of asthma.
Main Methods:
- Utilized ovalbumin (OVA)-induced asthma model in ICOSL knockout (KO) and wild-type (Wt) mice.
- Assessed lung eosinophil infiltration, histopathology, mucus production, and airway hyperresponsiveness.
- Analyzed serum antibody titers (IgG1, IgG2a, IgE) and T-cell cytokine production (T(h)1, T(h)2, T(h)17).
Main Results:
- ICOSL KO mice showed significantly reduced lung eosinophilia, inflammation, mucus, and airway hyperresponsiveness compared to Wt mice.
- Antigen-specific IgG1, IgG2a, and IgE antibody titers were lower in ICOSL KO mice.
- CD4(+) T cells from ICOSL KO mice produced less T(h)2 cytokines but more T(h)1 and IL-17 cytokines.
Conclusions:
- ICOSL plays a significant role in promoting allergic airway hyperresponsiveness.
- ICOSL enhances IgE antibody class switching and T(h)2 cytokine production.
- ICOSL diminishes T(h)17 responses and airway eosinophilia, contributing to asthma pathogenesis.
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