BackgroundChronic obstructive pulmonary disease (COPD) is a progressive and irreversible chronic inflammatory disease of the lung. The nature of the immune reaction in COPD raises the possibility that IL-17 and related cytokines may contribute to this disorder. This study analyzed the expression of IL-17A and IL-17F as well as the phenotype of cells producing them in bronchial biopsies from COPD patients.MethodsBronchoscopic biopsies of the airway were obtained from 16 COPD subjects (GOLD stage 1-4) and 15 control subjects. Paraffin sections were used for the investigation of IL-17A and IL-17F expression in the airways by immunohistochemistry, and frozen sections were used for the immunofluorescence double staining of IL-17A or IL-17F paired with CD4 or CD8. In order to confirm the expression of IL-17A and IL-17F at the mRNA level, a quantitative RT-PCR was performed on the total mRNA extracted from entire section or CD8 positive cells selected by laser capture microdissection.ResultsIL-17F immunoreactivity was significantly higher in the bronchial biopsies of COPD patients compared to control subjects (P < 0.0001). In the submucosa, the absolute number of both IL-17A and IL-17F positive cells was higher in COPD patients (P < 0.0001). After adjusting for the total number of cells in the submucosa, we still found that more cells were positive for both IL-17A (P < 0.0001) and IL-17F (P < 0.0001) in COPD patients compared to controls. The mRNA expression of IL-17A and IL-17F in airways of COPD patients was confirmed by RT-PCR. The expression of IL-17A and IL-17F was co-localized with not only CD4 but also CD8, which was further confirmed by RT-PCR on laser capture microdissection selected CD8 positive cells.ConclusionThese findings support the notion that Th17 cytokines could play important roles in the pathogenesis of COPD, raising the possibility of using this mechanism as the basis for novel therapeutic approaches.

Merkel cells are post-mitotic cells scattered throughout the epidermis of vertebrates. They are particularly interesting because of the close connections that they develop with sensory nerve endings and the number of peptides they can secrete. These features suggest that they may make an important contribution to skin homeostasis and cutaneous nerve development. However, these cells remain mysterious because they are difficult to study. They have not been successfully cultured and cannot be isolated, severely hampering molecular biology and functional analysis. Merkel cells probably originate in the neural crest of avians and mammalians, and their "spontaneous" appearance in the epidermis may be caused by a neuron-independent epidermal differentiation process. Their functions are still unclear: they take part in mechanoreception or at least interact with neurons, but little is known about their interactions with other epidermal cells. This review provides a new look at these least-known cells of the skin. The numerous peptides they synthesize and release may allow them to communicate with many cells other than neurons, and it is plausible that Merkel cells play a key role in skin physiology and physiopathology.

The efficacy of tacrolimus in pruritus, as well as the sensory side-effects, could be explained by a direct effect on neurons through an effect on calcineurin, possibly by a desensitization of TRPV1 and calcium currents through the PIP(2) regulation pathway.