Differential regulation of Th2 and Th1 lung inflammatory responses by protein kinase Cθ

Shahram Salek-Ardakani, Takanori So, Beth S. Halteman, Amnon Altman, Michael Croft

Research output: Contribution to journalArticlepeer-review

110 Citations (Scopus)

Abstract

In vitro and recent in vivo studies have identified protein kinase Cθ (PKCθ) as an important intermediate in signaling pathways leading to T cell activation, proliferation, and cytokine production. However, the importance of PKCθ to many T cell-driven inflammatory responses has not been demonstrated. In this study we show that although PKCθ is required for the development of a robust lung inflammatory response controlled by Th2 cells, it plays a lesser role in the development of a similar lung inflammatory response controlled by Th1 cells. PKCθ-deflcient mice were strongly compromised in generating Th2 cells and exhibited reduced airway eosinophilia and Th2 cytokine production in lungs. PKCθ was required for the initial development of Th1 cells, with these cells exhibiting delayed kinetics of differentiation and accumulation. However, with recall Ag challenge via the airways, this defect was overcome, and lung infiltration and Th1 cytokine production were largely unimpaired in PKCθ-deficient animals. These data suggest that PKCθ can play roles in aspects of both Th2 and Th1 responses, but lung inflammation induced by Th2 cells is more dependent on this protein kinase than lung inflammation induced by Th1 cells.

Original languageEnglish
Pages (from-to)6440-6447
Number of pages8
JournalJournal of Immunology
Volume173
Issue number10
DOIs
Publication statusPublished - 2004 Nov 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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