In vivo function of an interleukin 2 receptor β Chain (IL-2Rβ)/IL- 4Rα cytokine receptor chimera potentiates allergic airway disease

Jeehee Youn, Jin Chen, Shreevrat Goenka, Mark A. Aronica, Ana L. Mora, Victor Correa, James R. Sheller, Mark Boothby

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Strength of T cell receptor (TCR) signaling, coreceptors, costimulation, antigen-presenting cell type, and cytokines all play crucial roles in determining the efficiency with which type 2 T lymphocytes (Th2, Tc2) develop from uncommitted precursors. To investigate in vivo regulatory mechanisms that control the population of type 2 T cells and disease susceptibility, we have created lines of transgenic mice in which expression of a chimeric cytokine receptor (the mouse interleukin 2 receptor β chain [IL-2Rβ] extracellular domain fused to the cytoplasmic tail of IL-4Rα) is targeted to the T lymphoid lineage using the proximal lck promoter. This chimera transduced IL-4-specific signals in response to IL-2 binding and dramatically enhanced type 2 responses (IL-4, IL-5, and immunoglobulin E production) upon in vitro TCR stimulation or in vivo antigen challenge. Thus, type 2 effector function was augmented by IL-4 signals transduced through a chimeric receptor expressed in a T cell-specific manner. This influence was sufficient for establishment of antigen-induced allergic airway hyperresponsiveness on a disease-resistant background (C57BL/6).

Original languageEnglish
Pages (from-to)1803-1816
Number of pages14
JournalJournal of Experimental Medicine
Volume188
Issue number10
DOIs
StatePublished - 1998 Nov 16

Keywords

  • Allergic diseases
  • Interleukin 4
  • Signal transduction
  • T cell help

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