Airway infiltration of CD4+ CCR6+ Th17 type cells associated with chronic cigarette smoke induced airspace enlargement

Immunology Letters
Oliver J HarrisonPatrick T Walsh

Abstract

Recently, patients with tobacco smoke induced emphysema have been shown to exhibit classical signs of T cell mediated autoimmunity characterized by autoantibody production and Th1 type responses. As the recently described Th17 type subset has been found to play a role in the pathogenesis of a number of autoimmune diseases previously considered to be Th1 driven, we sought to examine whether a Th17 type response was associated with airspace enlargement in a murine model of emphysema. Six to eight months exposure of mice to inhalation of mainstream cigarette smoke led to progressive airspace enlargement as defined by morphometric analysis. Flow cytometric analysis of the bronchoalveolar lavage (BAL) from these mice demonstrated a significant increase in the overall number of both CD4+ and CD8+ T cells present. These cells were subsequently examined for skewing towards a Th1, Th2 or Th17 phenotype by intracellular cytokine analysis. Distinct populations of BAL CD4+ T cells were found to express IFN-gamma or IL-17 demonstrating the presence of both a Th1 and Th17 type response. No expression of the Th2 associated cytokine IL-4 was detected. Further analysis of this Th17 subset demonstrated that the majority of cells with this effect...Continue Reading

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