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ResearchIn-Press PreviewDermatologyImmunology Open Access | 10.1172/jci.insight.163495

Cellular mechanisms and effects of interleukin-4 receptor blockade in experimental conjunctivitis evoked by skin inflammation

Hongwei Han,1 Sheila Cummings,2 Kai-Ting C. Shade,3 Jennifer Johnson,2 George Qian,3 Joseph Gans,4 Srinivas Shankara,4 Javier M. Escobedo,4 Erik Zarazinski,5 Renee Bodinizzo,5 Dinesh S. Bangari,2 Paul Bryce,3 and Alexandra Hicks3

1Sanofi, Cambridge, United States of America

2Global Discovery Pathology, Sanofi, Framingham, United States of America

3Immunology and Inflammation Research Therapeutic Area, Sanofi, Cambridge, United States of America

4Translational Science Single Cell & Functional Genomics, Sanofi, Framingham, United States of America

5In-vivo Research Center, Sanofi, Framingham, United States of America

Find articles by Han, H. in: JCI | PubMed | Google Scholar

1Sanofi, Cambridge, United States of America

2Global Discovery Pathology, Sanofi, Framingham, United States of America

3Immunology and Inflammation Research Therapeutic Area, Sanofi, Cambridge, United States of America

4Translational Science Single Cell & Functional Genomics, Sanofi, Framingham, United States of America

5In-vivo Research Center, Sanofi, Framingham, United States of America

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1Sanofi, Cambridge, United States of America

2Global Discovery Pathology, Sanofi, Framingham, United States of America

3Immunology and Inflammation Research Therapeutic Area, Sanofi, Cambridge, United States of America

4Translational Science Single Cell & Functional Genomics, Sanofi, Framingham, United States of America

5In-vivo Research Center, Sanofi, Framingham, United States of America

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1Sanofi, Cambridge, United States of America

2Global Discovery Pathology, Sanofi, Framingham, United States of America

3Immunology and Inflammation Research Therapeutic Area, Sanofi, Cambridge, United States of America

4Translational Science Single Cell & Functional Genomics, Sanofi, Framingham, United States of America

5In-vivo Research Center, Sanofi, Framingham, United States of America

Find articles by Johnson, J. in: JCI | PubMed | Google Scholar

1Sanofi, Cambridge, United States of America

2Global Discovery Pathology, Sanofi, Framingham, United States of America

3Immunology and Inflammation Research Therapeutic Area, Sanofi, Cambridge, United States of America

4Translational Science Single Cell & Functional Genomics, Sanofi, Framingham, United States of America

5In-vivo Research Center, Sanofi, Framingham, United States of America

Find articles by Qian, G. in: JCI | PubMed | Google Scholar

1Sanofi, Cambridge, United States of America

2Global Discovery Pathology, Sanofi, Framingham, United States of America

3Immunology and Inflammation Research Therapeutic Area, Sanofi, Cambridge, United States of America

4Translational Science Single Cell & Functional Genomics, Sanofi, Framingham, United States of America

5In-vivo Research Center, Sanofi, Framingham, United States of America

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1Sanofi, Cambridge, United States of America

2Global Discovery Pathology, Sanofi, Framingham, United States of America

3Immunology and Inflammation Research Therapeutic Area, Sanofi, Cambridge, United States of America

4Translational Science Single Cell & Functional Genomics, Sanofi, Framingham, United States of America

5In-vivo Research Center, Sanofi, Framingham, United States of America

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1Sanofi, Cambridge, United States of America

2Global Discovery Pathology, Sanofi, Framingham, United States of America

3Immunology and Inflammation Research Therapeutic Area, Sanofi, Cambridge, United States of America

4Translational Science Single Cell & Functional Genomics, Sanofi, Framingham, United States of America

5In-vivo Research Center, Sanofi, Framingham, United States of America

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1Sanofi, Cambridge, United States of America

2Global Discovery Pathology, Sanofi, Framingham, United States of America

3Immunology and Inflammation Research Therapeutic Area, Sanofi, Cambridge, United States of America

4Translational Science Single Cell & Functional Genomics, Sanofi, Framingham, United States of America

5In-vivo Research Center, Sanofi, Framingham, United States of America

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1Sanofi, Cambridge, United States of America

2Global Discovery Pathology, Sanofi, Framingham, United States of America

3Immunology and Inflammation Research Therapeutic Area, Sanofi, Cambridge, United States of America

4Translational Science Single Cell & Functional Genomics, Sanofi, Framingham, United States of America

5In-vivo Research Center, Sanofi, Framingham, United States of America

Find articles by Bodinizzo, R. in: JCI | PubMed | Google Scholar

1Sanofi, Cambridge, United States of America

2Global Discovery Pathology, Sanofi, Framingham, United States of America

3Immunology and Inflammation Research Therapeutic Area, Sanofi, Cambridge, United States of America

4Translational Science Single Cell & Functional Genomics, Sanofi, Framingham, United States of America

5In-vivo Research Center, Sanofi, Framingham, United States of America

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1Sanofi, Cambridge, United States of America

2Global Discovery Pathology, Sanofi, Framingham, United States of America

3Immunology and Inflammation Research Therapeutic Area, Sanofi, Cambridge, United States of America

4Translational Science Single Cell & Functional Genomics, Sanofi, Framingham, United States of America

5In-vivo Research Center, Sanofi, Framingham, United States of America

Find articles by Bryce, P. in: JCI | PubMed | Google Scholar

1Sanofi, Cambridge, United States of America

2Global Discovery Pathology, Sanofi, Framingham, United States of America

3Immunology and Inflammation Research Therapeutic Area, Sanofi, Cambridge, United States of America

4Translational Science Single Cell & Functional Genomics, Sanofi, Framingham, United States of America

5In-vivo Research Center, Sanofi, Framingham, United States of America

Find articles by Hicks, A. in: JCI | PubMed | Google Scholar

Published January 10, 2023 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.163495.
Copyright © 2023, Han et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published January 10, 2023 - Version history
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Abstract

Ocular surface diseases, including conjunctivitis, are recognized as a common comorbidity in atopic dermatitis (AD) and also occur at an increased frequency in AD patients treated with biologics targeting interleukin-4 receptor alpha (IL-4Rα) or IL-13. However, the inflammatory mechanisms underlying this pathology are unknown. Here, we developed a novel mouse model of skin inflammation-evoked conjunctivitis and showed that it is dependent on CD4+ T cells and basophils. Blockade of IL-4Rα partially attenuated conjunctivitis development, downregulated basophil activation and led to a reduction in expression of genes related to type 2 cytokine responses. Together, these data suggest that an IL-4Rα-basophil axis plays a role in the development of murine allergic conjunctivitis. Interestingly, we found a significant augmentation of a number of genes that encode tear proteins and enzymes in anti-IL-4Rα-treated mice, which may underlie the partial efficacy in this model and may represent candidate mediators of the increased frequency of conjunctivitis following dupilumab in AD patients.

Version history
  • Version 1 (January 10, 2023): In-Press Preview
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