Chronic
inflammation is a key feature of many airway diseases. Leukocyte accumulation in the lung has the capacity to mediate many aspects of the pathophysiology of such diseases including
asthma and
chronic obstructive pulmonary disease (
COPD). Until recently, the CD4+ lymphocyte component of these inflammatory influxes was thought to consist of Th1 or Th2 type cells, however a third group of cells termed Th17 have been identified. These cells follow a distinct differentiation profile requiring
TGFbeta and
IL-6 leading to the expression of the Th17 selective
transcription factor,
RORgammat. Differentiation of these cells is restricted by Th1 and Th2
cytokines including IFNgamma and
IL-4 which attenuate Th17 cell differentiation. The presence of Th17 cells in the airway has yet to be confirmed, yet
IL-17 is expressed in both
asthma and
COPD. Many of the inflammatory effects of Th17 cells are attributed to the expression of this
cytokine. For example,
IL-17 up-regulates the expression of a number of CXCR2
chemokines including CXCL1, CXCL6 and CXCL8 together with neutrophil survival factors
GM-CSF and
G-CSF from the airway epithelium. This would suggest that Th17 cells are important in promoting and sustaining neutrophilic
inflammation as observed in severe
asthma and
COPD. In addition,
IL-17 can act synergistically with
viral infection or other inflammatory mediators including
TNF-alpha to potentiate these responses. Confirmation of the presence of Th17 cells in the airways in disease warrants further investigation since these cells would present a novel therapeutic opportunity to reduce neutrophilic
inflammation in the lung.