IL-17 mRNA in sputum of asthmatic patients: linking T cell driven inflammation and granulocytic influx?

Abstract

Background: The role of Th2 cells (producing interleukin (IL-)4, IL-5 and IL-13) in allergic asthma is well-defined. A distinct proinflammatory T cell lineage has recently been identified, called Th 17 cells, producing IL-17A, a cytokine that induces CXCL8 (IL-8) and recruits neutrophils. Neutrophilic infiltration in the airways is prominent in severe asthma exacerbations and may contribute to airway gland hypersecretion, bronchial hyper-reactivity and airway wall remodelling in asthma.

Potentiation of IL-19 expression in airway epithelia by IL-17A and IL-4/IL-13: Important implications in asthma

“…This is the first demonstration that a T H 2 cytokine can coordinate with a proinflammatory cytokine, such as IL-17A, to potentiate a T H 2 response. 11,18,[28][29][30][31] This discovery emphasizes the uniqueness of epithelia-derived IL-19 in allergic diseases and suggests important roles for IL-13 and IL-17A in IL-19 regulation. [32][33][34] We hypothesize that airway epithelial IL-19 is induced by IL-17A and T H 2 cytokines, mainly IL-13, to further potentiate a T H 2-dominant response in a positive feedback manner in the context of allergic airway diseases, such as asthma.…”

“…[32][33][34][35][36] IL-17A also plays a role in human asthmatic patients and in airways of allergic animals. 18,28,30,[37][38][39] Studies have found that in patients with moderate-to-severe asthma, neutrophils are found to be more abundant than eosinophils in the bronchoalveolar lavage fluid. 30,31,40 IL-17A can promote neutrophil recruitment, which might contribute to certain asthmatic phenotypes characterized by both high neutrophil counts and IL-17A expression.…”

Interleukin-17 cytokine signalling in patients with asthma

“…A true correlation between IL-17A and neutrophils was demonstrated by BULLENS et al [38] when assessing mRNA for IL-17A in sputum cells from patients with mild and moderate-to-severe asthma. However, the increase in this mRNA was modest compared with healthy control subjects but the results did not suggest that the transcription of IL-17A is sensitive to treatment with inhaled glucocorticoids.…”

Enhanced production of IL-17A in patients with severe asthma is inhibited by 1α,25-dihydroxyvitamin D3 in a glucocorticoid-independent fashion

“…Thus IL-17A expression in sputum or bronchial mucosal biopsies has been correlated with bronchial hyperresponsiveness (16), Nanzer et al 5 granulocyte infiltration (17) and production of fibrogenic mediators by bronchial fibroblasts (18).…”