Antagonism of airway tolerance by endotoxin/lipopolysaccharide through promoting OX40L and suppressing antigen-specific Foxp3+ T regulatory cells

Wei Duan, Takanori So, Michael Croft

研究成果: Article査読

61 被引用数 (Scopus)

抄録

Respiratory exposure to allergens can lead to airway tolerance. Factors that antagonize tolerance mechanisms in the lung might result in susceptibility to diseases such as asthma. We show that inhalation of endotoxin/LPS with Ag prevented airway tolerance and abolished protection from T cell-driven asthmatic lung inflammation. Under conditions leading to tolerance, adaptive Agspecific CD4+Foxp3+ T regulatory cells (Treg) were generated following exposure to intranasal Ag and outnumbered IL-4- and IFN-γ-producing CD4 T cells by 100:1 or greater. Inhaled LPS altered the ratio of Treg to IL-4+ or IFN-γ+ T cells by concomitantly suppressing Treg generation and promoting effector T cell generation. LPS induced OX40L expression on dendritic cells and B cells that resulted in a synergistic activity between TLR4 and OX40 signals, leading to production of IL-4, IFN-γ, and IL-6, which blocked Treg development. Furthermore, inhibiting OX40/OX40L interactions prevented LPS from suppressing tolerance, and resulted in the generation of greater numbers of adaptive Treg. Thus, cooperation between TLR4 and OX40 controls susceptibility to developing airway disease via modulating the balance between adaptive Treg and IL-4 + or IFN-γ+ T cells. Targeting OX40L then has the potential to improve the efficacy of Ag immunotherapy to promote tolerance.

本文言語English
ページ(範囲)8650-8659
ページ数10
ジャーナルJournal of Immunology
181
12
DOI
出版ステータスPublished - 2008 12 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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