1-Minute Summary: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and receptors in type 1, type 2 and type 17 inflammation in cross-sectional asthma study

Expert Name
Dr Michelle Marks
Expert Affiliation
Department of Internal Medicine, Pulmonary Section, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA

Marks M, et al. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and receptors in type 1, type 2 and type 17 inflammation in cross-sectional asthma study. Thorax 2020;0:1–4. Epub

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has a potential role in allergic asthma [1,2]. TRAIL induces apoptosis in a variety of cells thereby resolving inflammation [1,3]. Conversely, TRAIL has been shown to promote eosinophil survival in patients with asthma following segmental antigen challenge, thus resolving asthma inflammation [2]. These counteracting effects suggest divergent roles for TRAIL in lung diseases [4].

Subjects with asthma were divided into high and low TRAIL groups. Samples were obtained from sputum, bronchoalveolar lavage, and bronchoscopy biopsies. High TRAIL subjects had lower maximal forced expiratory volume in 1 second (FEV1) percentage predicted compared with low TRAIL subjects (P=0.043), indicating lower lung function. Moreover, the high TRAIL group had a greater proportion of subjects with exacerbations provoked by physical activity (P=0.050). Increases in leukocytes were found in the high TRAIL group (P<0.001), associated with increased inflammatory proteins, including type 1, type 2, and type 17 cytokines. However, no increase in interleukin 9 was observed. Sputum cells had increased TRAIL decoy receptor R3/DcR1 compared with death receptor R1/DR4 (P=0.006) (see Figure), suggesting reduced apoptosis and prolonged cellular inflammation [3]. This may prolong airway inflammation, even in stable disease state. Higher sputum TRAIL levels were associated with 2 specific alleles for known single nucleotide polymorphisms (SNPs) in the TRAIL gene, providing further support to haplotype analysis associating TRAIL with asthma [5].

In conclusion, TRAIL appears associated with lower lung function and increased healthcare utilisation [6], characteristics typical for more severe asthma.


1. Faustino L, et al. Tumor necrosis factor-related apoptosis-inducing ligand mediates the resolution of allergic airway inflammation induced by chronic allergen inhalation. Mucosal Immunol 2014;7:1199–208.

2. Robertson NM, et al. Differential expression of TRAIL and TRAIL receptors in allergic asthmatics following segmental antigen challenge: evidence for a role of TRAIL in eosinophil survival. J Immunol 2002;169:5986–96.

3. McGrath EE, et al. Tnf-Related apoptosis-inducing ligand (TRAIL) regulates inflammatory neutrophil apoptosis and enhances resolution of inflammation. J Leukoc Biol 2011;90:855–65.

4. Braithwaite AT, et al. Divergent roles for TRAIL in lung diseases. Front Med 2018;5:212.

5. Weckmann M, et al. Haplotypes covering the TNFSF10 gene are associated with bronchial asthma. Pediatr Allergy Immunol 2011;22:25–30.

6. Moore WC, et al. Characterization of the severe asthma phenotype by the National heart, lung, and blood Institute’s severe asthma research program. J Allergy Clin Immunol 2007;119:405–13.

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