Targeting the human βc Receptor inhibits contact dermatitis in a transgenic mouse model
Date
2022
Authors
Yip, K.H.
McKenzie, D.
Ramshaw, H.S.
Chao, J.
McClure, B.J.
Raquet, E.
Kraushaar, T.
Röder, J.
Maxwell, M.
Alhamdoosh, M.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Journal of Investigative Dermatology, 2022; 142(4):1103-1113
Statement of Responsibility
Kwok Ho Yip ... Barbara J. McClure ... Angel F. Lopez ... Harshita Pant ... Hayley S. Ramshaw ... et. al
Conference Name
Abstract
Allergic contact dermatitis (ACD) is a prevalent and poorly controlled inflammatory disease caused by skin infiltration of T cells and granulocytes. The beta common (bc) cytokines GM-CSF, IL-3, and IL-5 are powerful regulators of granulocyte function that signal through their common receptor subunit bc, a property that has made bc an attractive target to simultaneously inhibit these cytokines. However, the species specificity of bc has precluded testing of inhibitors of human bc in mouse models. To overcome this problem, we developed a human bc receptor transgenic mouse strain with a hematopoietic cell‒specific expression of human bc instead of mouse bc. Human bc receptor transgenic cells responded to mouse GM-CSF and IL-5 but not to IL-3 in vitro and developed tissue pathology and cellular inflammation comparable with those in wild-type mice in a model of ACD. Similarly, Il3e/e mice developed ACD pathology comparable with that of wild-type mice. Importantly, the blocking antiehuman bc antibody CSL311 strongly suppressed ear pinna thickening and histopathological changes typical of ACD and reduced accumulation of neutrophils, mast cells, and eosinophils in the skin. These results show that GM-CSF and IL-5 but not IL-3 are major mediators of ACD and define the human bc receptor transgenic mouse as a unique platform to test the inhibitors of bc in vivo.
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Dissertation Note
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Description
Data source: Supplementary material, https://doi.org/10.1016/j.jid.2021.07.183
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© 2021 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology