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Pulmonary Infiltration of CCR6+ve CD4+ Th17 type cells associated with chronic cigarette smoke induced airspace enlargement
Author(s) -
Harrison Oliver James,
Podolin Patricia,
Bolognese Brian,
Foley Joseph,
Long Edward,
Walsh Patrick T
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.486
Subject(s) - immunology , bronchoalveolar lavage , c c chemokine receptor type 6 , pathogenesis , cytokine , autoimmunity , interleukin 17 , chemokine , medicine , cxcr3 , t cell , inflammation , chemokine receptor , lung , immune system
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 months exposure of mice to inhalation of mainstream cigarette smoke led to a significant degree of 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 total and CD4+ 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‐γ 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 a strong association between expression of the chemokine receptor CCR6 and the ability to express IL‐17. Together these data identify a novel T cell subset associated with pulmonary inflammation as a result of cigarette smoke exposure. Given the reported roles of CCR6 and IL‐17 in promoting pulmonary inflammatory responses this subset may play an important role in the pathogenesis of cigarette smoke induced autoimmunity.