Fas-positive T cells regulate the resolution of airway inflammation in a murine model of asthma

Jiankun Tong, Hozefa S. Bandulwala, Bryan S. Clay, Robert A. Anders, Rebecca A. Shilling, Diwakar D. Balachandran, Bohao Chen, Joel V. Weinstock, Julian Solway, Kimm J. Hamann, Anne I. Sperling

Research output: Contribution to journalArticlepeer-review

Abstract

Persistent airway inflammation, mucus production, and airway hyperreactivity are the major contributors to the frequency and severity of asthma. Why lung inflammation persists in asthmatics remains unclear. It has been proposed that Fas-mediated apoptosis of inflammatory cells is a fundamental mechanism involved in the resolution of eosinophilic airway inflammation. Because infiltrating eosinophils are highly sensitive to Fas-mediated apoptosis, it has been presumed that direct ligation of Fas on eosinophils is involved. Here, we utilize adoptive transfers of T cells to demonstrate that the delayed resolution of eosinophilia in Fas-deficient mice is a downstream effect of Fas deficiency on T cells, not eosinophils. Interestingly, the mice that received Fas-deficient T cells, but not the controls, developed a persistent phase of inflammation that failed to resolve even 6 wk after the last challenge. This persistent phase correlated with decreased interferon (IFN)γ production by Fas-deficient T cells and could be reproduced with adoptive transfer of IFNγ-deficient T cells. These data demonstrate that Fas deficiency on T cells is sufficient for the development of long-term allergic airway disease in mice and implies that deregulation of death receptors such as Fas on human T cells could be an important factor in the development and/or chronic nature of asthma. JEM

Original languageEnglish (US)
Pages (from-to)1173-1184
Number of pages12
JournalJournal of Experimental Medicine
Volume203
Issue number5
DOIs
StatePublished - May 15 2006
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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