PURPOSE: Asthma is characterized by airway hyperreactivity (AHR) and T helper type 2 (Th2)-driven inflammatory responses. In addition to Th2 cells, other T cell subsets are involved in the pathogenesis of asthma such as invariant Natural Killer T cells (iNKTs). These iNKT cells have been found to be present in bronchoalveolar lavage (BAL) of patients with severe asthma and when stimulated produce significant amount of IL-4 and IL-13. We recently reported that the cytokine IL-25 was critical for the development of AHR in animal models of asthma. The CD4+ iNKTs were found to express IL17-RB, the receptor for IL-25 (1). The purpose of our study was to identify iNKT cells in the BAL of patients with severe asthma and determine whether IL-17RB is also expressed in these cells . Hypothesis: The results found in the mouse model suggest that IL-17RB+ iNKT cells may also play a crucial role in the pathogenesis of severe asthmatic patients.
METHODS: We performed bronchoscopy with BAL on seven hospitalized severe asthmatics ( five intubated patients and two non Intubated patients). BAL specimens were analyzed for the expression of IL-17RB on iNKTs using eight color flow cytometry which was gated on the BAL CD3+ cells.
RESULTS: iNKT cells and their subsets were detected in the BAL of patients with severe asthma. Approximately 1-3% of the CD4+ iNKT cells expressed IL-17RB.The IL-17RB was not detected on CD8+ iNKT cells.
CONCLUSIONS: This pilot study of seven severe asthma patients suggest that the IL-17RB expression is confined to the CD4 population of iNKT cells.Further studies with greater number of subjects and controls are planned to validate these initial observations. 1. Stock, P et al , j immunoly 2009; 182: 5116-5122
CLINICAL IMPLICATIONS: The mechanistic role of iNKT cells in asthma is unclear but our observation adds to a growing body of evidence in humans supporting the hypothesis that iNKT cells might play an important role in the development of severe asthma
DISCLOSURE: The following authors have nothing to disclose: Jooby Babu, Vincent Lombardi, Omid Akbari, Richard Barbers
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