An international research collaboraration between the laboratory of Prof. Padraic Fallon in Trinity College Dublin, Ireland with researchers in the University of Edinburgh and the University of Erlangen has uncovered a potential new mechanism behind development of idiopathic pulmonary fibrosis (IPF). The study, published recently in the Proceedings of the National Academy of Sciences (PNAS) has identified the cytokine IL-25 and the novel immune cell type, the type 2 innate lymphoid cell (ILC2) as previously unsuspected players in development of IPF.
IPF is a distressing condition whereby lungs of patients become irreversibly scarred, leading to difficulty in breathing. The condition is chronic and progressive with a poor prognosis due to the lack of understanding of the underlying mechanisms and hence lack of effective therapies. Thus research efforts to advance understanding of this condition are all the more important. The disease has been linked to factors such as cigarette smoking and occupational exposure to substances such as gases and dust. It can also arise as a complication of other pulmonary diseases such as asthma. Current hypotheses suggest that the scarring is a result of repeated injuries to the alveolar epithelial cells resulting in release of pro-fibrotic regulators including transforming growth factor β (TGF β), which results in a knock-on effect on fibroblasts, which produce collagen, leading to the scarring.
The PNAS study used both in vivo mouse models and lung samples from patients with IPF in order to examine the mechanisms of IPF. The murine models implicated IL-25 as a major player in IPF generation. The mechanism identified involved IL-25 mediated release of IL-13 from ILC2 cells directly resulting in collagen deposition in the lungs of the challenged mice. In order to link the findings to human disease, lung samples were collected from IPF patients. Interestingly, these samples had increased expression of IL-25 when compared to control samples and also featured a population of ILC2 cells that was missing from control samples. The authors of the study concluded that their findings suggest an innate, T-cell independent mechanism for IPF generation that opens up previously unsuspected therapeutic avenues targeting IL-25 and ILC2.
IPF is not the only disease identified by Prof. Fallon’s research group to potentially feature ILC2 cells and IL-25. In a collaboration with researchers in the University of Oxford, UK and LMB Cambridge, UK, they published a recent study in The Journal of Experimental Medicine implicating ILC2 and IL-25 in the development of atopic dermatitis (eczema) while the first author of the PNAS paper, Dr. Emily Hams, is also examining their role in regulation of obesity. Thus targeting of IL-25 and ILC2 may have far-reaching implications for new therapies for a wide range of diseases.
Sources
Press release:http://www.sfi.ie/news-resources/press-releases/scientists-discover-new-cellular-process-leading-to-lung-fibrosis.html [Accessed 10 February 2014].
HAMS, E., ARMSTRONG, M., BARLOW, J., SAUNDERS, S., SCHWARTZ, C., COOKE, G., FAHY, R.J., CROTTY, T.B., HIRANI, N., FLYNN, R.J., VOEHRINGER, D., MCKENZIE, A.N., DONNELLY, S.C. and FALLON, P. (2014). IL-25 and type 2 innate lymphoid cells induce pulmonary fibrosis. Proceedings Of The National Academy Of Sciences Of The United States Of America, 111(1), 367-372. doi:10.1073/pnas.1315854111
SALIMI, M., BARLOW, J., SAUNDERS, S., XUE, L., GUTOWSKA-OWSIAK, D., WANG, X., HUANG, L., JOHNSON, D., SCANLON, S., MCKENZIE, A., FALLON, P., and OGG, G 2013, A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis. The Journal Of Experimental Medicine, 210, 13, pp. 2939-2950
IPF is a distressing condition whereby lungs of patients become irreversibly scarred, leading to difficulty in breathing. The condition is chronic and progressive with a poor prognosis due to the lack of understanding of the underlying mechanisms and hence lack of effective therapies. Thus research efforts to advance understanding of this condition are all the more important. The disease has been linked to factors such as cigarette smoking and occupational exposure to substances such as gases and dust. It can also arise as a complication of other pulmonary diseases such as asthma. Current hypotheses suggest that the scarring is a result of repeated injuries to the alveolar epithelial cells resulting in release of pro-fibrotic regulators including transforming growth factor β (TGF β), which results in a knock-on effect on fibroblasts, which produce collagen, leading to the scarring.
The PNAS study used both in vivo mouse models and lung samples from patients with IPF in order to examine the mechanisms of IPF. The murine models implicated IL-25 as a major player in IPF generation. The mechanism identified involved IL-25 mediated release of IL-13 from ILC2 cells directly resulting in collagen deposition in the lungs of the challenged mice. In order to link the findings to human disease, lung samples were collected from IPF patients. Interestingly, these samples had increased expression of IL-25 when compared to control samples and also featured a population of ILC2 cells that was missing from control samples. The authors of the study concluded that their findings suggest an innate, T-cell independent mechanism for IPF generation that opens up previously unsuspected therapeutic avenues targeting IL-25 and ILC2.
IPF is not the only disease identified by Prof. Fallon’s research group to potentially feature ILC2 cells and IL-25. In a collaboration with researchers in the University of Oxford, UK and LMB Cambridge, UK, they published a recent study in The Journal of Experimental Medicine implicating ILC2 and IL-25 in the development of atopic dermatitis (eczema) while the first author of the PNAS paper, Dr. Emily Hams, is also examining their role in regulation of obesity. Thus targeting of IL-25 and ILC2 may have far-reaching implications for new therapies for a wide range of diseases.
Sources
Press release:http://www.sfi.ie/news-resources/press-releases/scientists-discover-new-cellular-process-leading-to-lung-fibrosis.html [Accessed 10 February 2014].
HAMS, E., ARMSTRONG, M., BARLOW, J., SAUNDERS, S., SCHWARTZ, C., COOKE, G., FAHY, R.J., CROTTY, T.B., HIRANI, N., FLYNN, R.J., VOEHRINGER, D., MCKENZIE, A.N., DONNELLY, S.C. and FALLON, P. (2014). IL-25 and type 2 innate lymphoid cells induce pulmonary fibrosis. Proceedings Of The National Academy Of Sciences Of The United States Of America, 111(1), 367-372. doi:10.1073/pnas.1315854111
SALIMI, M., BARLOW, J., SAUNDERS, S., XUE, L., GUTOWSKA-OWSIAK, D., WANG, X., HUANG, L., JOHNSON, D., SCANLON, S., MCKENZIE, A., FALLON, P., and OGG, G 2013, A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis. The Journal Of Experimental Medicine, 210, 13, pp. 2939-2950
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