Role of interleukin-17F in chronic inflammatory and allergic lung disease
Article first published online: 4 SEP 2006
Clinical & Experimental Allergy
Volume 36, Issue 9, pages 1109–1114, September 2006
How to Cite
Hizawa, N., Kawaguchi, M., Huang, S.-K. and Nishimura, M. (2006), Role of interleukin-17F in chronic inflammatory and allergic lung disease. Clinical & Experimental Allergy, 36: 1109–1114. doi: 10.1111/j.1365-2222.2006.02550.x
- Issue published online: 4 SEP 2006
- Article first published online: 4 SEP 2006
- Submitted 1 February 2006; revised 18 April 2006; accepted 21 June 2006.
IL-17 family members belong to a distinct category of cytokines that coordinate local tissue inflammation by inducing the release of pro-inflammatory and neutrophil-mobilizing cytokines. The importance of the IL-17 family in inflammatory and autoimmune disease is becoming increasingly apparent. IL-17F is a recently discovered member of the IL-17 family that has a number of biological activities through induction of various cytokines, chemokines, and mediators. IL-17A, the founding member of the IL-17 family, and IL-17F are produced by several inflammatory cells, including activated T cells, in response to infectious and antigenic stimuli. Overexpression of IL-17A or IL-17F in the lungs results in induction of CXC chemokines and neutrophil recruitment. In a case–control study of 1125 unrelated Japanese subjects, a His161 to Arg161 (H161R) substitution in the third exon of the IL17F gene was shown to be associated with asthma and chronic obstructive pulmonary disease (COPD). Functionally, this variant failed to induce cytokines and chemokines, and interestingly, was able to antagonize the activity of wild-type IL-17F. These results provide an experimental basis for the observed genetic association with chronic inflammatory lung diseases, and also suggest the potential therapeutic utility of this antagonistic variant of IL-17F. Given that asthma and COPD are complex diseases involving a number of genetic and environmental factors, the genetic impact of IL-17F H161R with regard to the development of chronic airway inflammation likely varies among individuals with different genetic backgrounds and environmental exposures.