Requirement for the p75 TNF-α receptor 2 in the regulation of airway hyperresponsiveness by γδ T cells

Arihiko Kanehiro, Michael Lahn, Mika J. Mäkelä, Azzeddine Dakhama, Anthony Joetham, Yeong Ho Rha, Willi Born, Erwin W. Gelfand

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30 Citations (Scopus)

Abstract

In a recent study, we found that TNF-α negatively regulates airway responsiveness through the activation of γδ T cells. The biological activities of TNF-α are mediated by two structurally related but functionally distinct receptors, p55 (TNFR1) and p75 (TNFR2), which are independently expressed on the cell surface. However, the relative importance of either TNFR in airway hyperresponsiveness (AHR) is unknown. To investigate the importance of these TNFRs in the development of allergen-induced AHR, p55-deficient and p75-deficient mice were sensitized to OVA by i.p. injection and subsequently challenged with OVA via the airways; airway responsiveness to inhaled methacholine was monitored. p75-deficient mice developed AHR to a similar degree as control mice. In contrast, p55-deficient mice, which were sensitized and challenged with OVA, failed to develop AHR. In p55-deficient mice, both the numbers of eosinophils and levels of IL-5 in bronchoalveolar lavage fluid were significantly lower than in sensitized/challenged control mice (p < 0.05). However, depletion of γδ T cells resulted in significant increases in AHR in the p55-deficient mice, whereas no significant effect of γδ T cell depletion was evident in the p75-deficient mice. These data indicate that, in the absence of TNFR1 (p55), where TNF-α uses the p75 pathway exclusively, the development of AHR is regulated by γδ T cells.

Original languageEnglish
Pages (from-to)4190-4197
Number of pages8
JournalJournal of Immunology
Volume169
Issue number8
Publication statusPublished - Oct 15 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Kanehiro, A., Lahn, M., Mäkelä, M. J., Dakhama, A., Joetham, A., Rha, Y. H., Born, W., & Gelfand, E. W. (2002). Requirement for the p75 TNF-α receptor 2 in the regulation of airway hyperresponsiveness by γδ T cells. Journal of Immunology, 169(8), 4190-4197.