TNF-α/IL-17 synergy inhibits IL-13 bioactivity via IL-13Rα2 induction

Vahe Badalyan; Robert Thompson; Kezia Addo; Lee A Borthwick; Andrew J Fisher; Tatiana Ort; Timothy G Myers; Thomas A Wynn; Thirumalai R Ramalingam

doi:10.1016/j.jaci.2014.05.019

TNF-α/IL-17 synergy inhibits IL-13 bioactivity via IL-13Rα2 induction

J Allergy Clin Immunol. 2014 Oct;134(4):975-8.e5. doi: 10.1016/j.jaci.2014.05.019. Epub 2014 Jun 20.

Authors

Vahe Badalyan¹, Robert Thompson², Kezia Addo², Lee A Borthwick³, Andrew J Fisher³, Tatiana Ort⁴, Timothy G Myers⁵, Thomas A Wynn², Thirumalai R Ramalingam⁶

Affiliations

¹ Immunopathogenesis Section, National Institute of Allergy and Infectious Disease, Bethesda, Md; Division of Gastroenterology, Hepatology, and Nutrition, Children's National Medical Center, Washington, DC.
² Immunopathogenesis Section, National Institute of Allergy and Infectious Disease, Bethesda, Md.
³ Tissue Fibrosis and Repair Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
⁴ Janssen R&D Companies of Johnson & Johnson, Springhouse, Pa.
⁵ Genomic Technologies Section, National Institute of Allergy and Infectious Disease, Bethesda, Md.
⁶ Immunopathogenesis Section, National Institute of Allergy and Infectious Disease, Bethesda, Md. Electronic address: ramalingamt@niaid.nih.gov.

Abstract

IL-17 and TNFα synergistically induce surface expression of IL-13Rα2 on primary lung fibroblasts, rendering them unresponsive to IL-13. Neutralizing antibodies to IL-13Rα2 restored IL-13-mediated signaling and transcriptome studies confirmed IL-13Rα2 is an IL-13 decoy receptor.

Publication types

Letter
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Asthma / immunology*
Asthma / therapy
Cells, Cultured
Fibroblasts / immunology*
Humans
Immunotherapy
Interleukin-13 / immunology*
Interleukin-13 Receptor alpha2 Subunit / genetics
Interleukin-13 Receptor alpha2 Subunit / metabolism*
Interleukin-17 / immunology*
Interleukin-4 / immunology
Lung / pathology*
Mice
Molecular Targeted Therapy
Tumor Necrosis Factor-alpha / immunology*
Up-Regulation

Substances

Interleukin-13
Interleukin-13 Receptor alpha2 Subunit
Interleukin-17
Tumor Necrosis Factor-alpha
Interleukin-4

Grants and funding

Z99 AI999999/Intramural NIH HHS/United States