Immunostimulatory oligonucleotides block allergic airway inflammation by inhibiting Th2 cell activation and IgE-mediated cytokine induction

Edith M. Hessel, Mabel Chu, Jennifer O. Lizcano, Bonnie Chang, Nancy Herman, Sariah A. Kell, Marsha Wills-Karp, Robert L. Coffman

Research output: Contribution to journalArticlepeer-review

Abstract

A single treatment with a CpG-containing immunostimulatory DNA sequence (ISS) given before allergen challenge can inhibit T helper type 2 cell (Th2)-mediated airway responses in animal models of allergic asthma; however, the mechanism of this inhibition remains largely undefined. Here, we demonstrate that airway delivery of ISS before allergen challenge in Th2-primed mice acts in two distinct ways to prevent the allergic responses to this challenge. The first is to prevent induction of cytokines from allergen-specific Th2 cells, as demonstrated by the nearly complete inhibition of Th2 cytokine production, Th2-dependent functional responses, and gene induction patterns. ISS inhibits the Th2 response by rendering lung antigen-presenting cells (APCs) unable to effectively present antigen to Th2 cells, but not to Th1 cells. This loss of APC function correlates with a reduced expression of costimulatory molecules, including programmed cell death ligand (PD-L)1, PD-L2, CD40, CD80, CD86, and inducible T cell costimulator, and of major histocompatibility complex class II on CD11c+ APCs from the airways of ISS-treated mice. The second important action of ISS is inhibition of immunoglobulin E-dependent release of Th2 cytokines, especially interleukin 4, from basophils and/or mast cells in the airways of Th2-primed mice. Thus, inhibition by ISS of allergic responses can be explained by two novel mechanisms that culminate in the inhibition of the principal sources of type 2 cytokines in the airways. JEM

Original languageEnglish (US)
Pages (from-to)1563-1573
Number of pages11
JournalJournal of Experimental Medicine
Volume202
Issue number11
DOIs
StatePublished - Dec 5 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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