University of Tasmania
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Peripheral immune cell abnormalities associated with cystic fibrosis

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posted on 2023-05-26, 05:36 authored by Mulcahy, EM
Cystic fibrosis (CF) is the most common life-limiting single-gene disease. It is caused by mutations to the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is expressed on immune cells such as dendritic cells, monocytes/macrophages and lymphocytes. Lack of CFTR expression on lymphocytes and monocytes/macrophages has been reported to result in abnormal immune responses. An unresolving hyperinflammatory and T helper (Th)2/Th17 skewed immune response has also been reported in CF. We therefore hypothesised that abnormalities in both the innate and adaptive immune responses may play a pivotal role in the pathogenesis of CF lung disease. Peripheral blood mononuclear cells (PBMC) isolated from people with CF, CF carriers and healthy age-matched controls were stained with antibodies for identification of CD4\\(^+\\) effector (Th1, Th2, Th17) and T regulatory (Treg) (FOXP3\\(^+\\) Treg, IL-10\\(^+\\) T regulatory 1 [Tr1], transforming growth factor (TGF)˜í‚â§\\(^+\\) Th3) cells, na‚àövòve/memory CD4\\(^+\\) and Treg cells expressing the Th1-, Th2- and Th17-associated homing markers (CXCR3, CCR4, CCR6) and innate immune cell populations including natural killer (NK) cells, monocytes, dendritic cells (DC) and myeloid derived suppressor cells (MDSC) using multicolour flow cytometric analysis. Gene expression of the main transcription regulators of CD4\\(^+\\) subsets and of inflammatory markers was also measured using reverse transcription‚Äö-quantitative polymerase chain reaction (RT-qPCR). Subtle changes were observed in T cell subset proportions in CF peripheral blood, with a detectable Th2 bias and a link between poor lung function and high Th17 percent. All innate immune cell proportions were altered in CF compared with healthy controls, and percentages of NK and MDSC were also correlated with lung function. CF carriers, who have only one mutated CFTR copy, presented with an immune phenotype similar to CF patients or intermediate between those of controls and CF patients. Because the CF carriers did not have chronic infections, this suggested that the many of the abnormal immune responses seen in people with CF may be the consequence of defective CFTR rather than of chronic infection. These findings suggest that greater emphasis should be placed on treating aberrant immune responses in CF.


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Copyright 2017 the author The author has published an article base on chapter 3. It is: Mulcahy, E. M., Hudson, J. B., Beggs, S. A., Reid, D. W., Roddam, L. F., Cooley, M. A. 2015. High peripheral blood Th17 percent associated with poor lung function in cystic fibrosis, PLoS one 10(3): e0120912. It is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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