Series Explores Key Players in ‘Complex Puzzle’ of Cystic Fibrosis

The Journal of Innate Immunity published three studies that reviewed several central questions about lung disease in cystic fibrosis (CF). The reviews, prepared by three international opinion research leaders in the field, attempt to shed light on some still unclear aspects of this disease.

These reviews “will help to consolidate our mechanistic understanding of the networks in innate immunity, with the final aim to assess their diagnostic and therapeutic applicability in CF lung disease,” wrote Hasan-Halit Öz, MD, and Dominik Hartl, MD, PhD, in an editorial summarizing the review series published in the journal’s August issue. The editorial is titled “Innate Immunity in Cystic Fibrosis: Novel Pieces of the Puzzle.”

What is curious about CF lung disease is the complex interaction between the impairment of the cleaning function of airway epithelial cells, the accumulation of innate immune cells, and lung infection by microbes (mainly bacteria and fungi).

The complex relationship between these factors has made it difficult to understand several aspects of the disease, such as whether the innate inflammatory response in CF lung disease is a friend or foe, which innate immune cells are protective and which harmful, and those receptors or molecular pathways that might become therapeutic targets to regulate innate immunity in CF.

According to the editorial, the review series covers relevant topics in CF lung disease, such as “the key players in the innate immune response in the context of the CF lung … as well as … the major innate immune cells that migrate into the inflamed CF microenvironment.” It also looks at “the key players regulating host-pathogen interactions in infective CF lung disease” and the “complex topic of macrophage [components of the immune system] plasticity and functionality in CF lung disease, a promising though controversial field of research.”

The authors concluded: “Summarizing the studies in the field of innate immunity in CF lung disease reveals the emergence of new players, i.e. microRNAs, novel pathogen-sensing pathways, specialized immune cell subsets, e.g. innate lymphoid cells and myeloid-derived suppressor cells, and the microbiome. All of these, in combination, add several layers of complexity to the puzzle of innate immunity and inflammation in CF lung disease.

“Comparative studies using in vitro and in vivo (focus: mouse, ferret and pig) approaches as well as biomarker readouts from clinical trials will help to consolidate our mechanistic understanding of the networks in innate immunity, with the final aim to assess their diagnostic and therapeutic applicability in CF lung disease.”

According to the authors, there are other topics of interest that, although not covered in this series, might be of interest to CF patients and researchers, such as novel anti-inflammatory therapeutic approaches, the microbiome, and the role of certain components of the immune system (namely neutrophils) and the chemokine system.

CF is a genetic disorder caused by mutations in the gene cystic fibrosis transmembrane conductance regulator (CFTR). Mutations in this gene are responsible for the accumulation of mucus in several organs, mainly the lungs but also the pancreas, liver, kidneys, and intestines, which allows microbes to grow in a non-longer sterile surface and gradually impair the working of these organs.

Mortality among CF patients is mostly related to lung complications, such as chronic airway infections and inflammation.