Interleukin‐17A and interleukin‐22 production by conventional and non‐conventional lymphocytes in three different end‐stage lung diseases

Abstract

Objectives The contribution of adaptive vs. innate lymphocytes to IL‐17A and IL‐22 secretion at the end stage of chronic lung diseases remains largely unexplored. In order to uncover tissue‐ and disease‐specific secretion patterns, we compared production patterns of IL‐17A and IL‐22 in three different human end‐stage lung disease entities. Methods Production of IL‐17A, IL‐22 and associated cytokines was assessed in supernatants of re‐stimulated lymphocytes by multiplex assays and multicolour flow cytometry of conventional T cells, iNKT cells, γδ T cells and innate lymphoid cells in bronchial lymph node and lung tissue from patients with emphysema ( n = 19), idiopathic pulmonary fibrosis ( n = 14) and cystic fibrosis ( n = 23), as well as lung donors ( n = 17). Results We detected secretion of IL‐17A and IL‐22 by CD4 + T cells, CD8 + T cells, innate lymphoid cells, γδ T cells and iNKT cells in all end‐stage lung disease entities. Our analyses revealed disease‐specific contributions of individual lymphocyte subpopulations to cytokine secretion patterns. We furthermore found the high levels of microbial detection in CF samples to associate with a more pronounced IL‐17A signature upon antigen‐specific and unspecific re‐stimulation compared to other disease entities and lung donors. Conclusion Our results show that both adaptive and innate lymphocyte populations contribute to IL‐17A‐dependent pathologies in different end‐stage lung disease entities, where they establish an IL‐17A‐rich microenvironment. Microbial colonisation patterns and cytokine secretion upon microbial re‐stimulation suggest that pathogens drive IL‐17A secretion patterns in end‐stage lung disease.

Impact of elexacaftor–tezacaftor–ivacaftor on bacterial colonization and inflammatory responses in cystic fibrosis

“…Associations between decreased neutrophil, IL‐8, and IL‐17A levels suggest CFTR modulators may reduce neutrophilic inflammation and, perhaps neutrophil‐mediated lung damage. These findings agree with a recent study that compared CF, lung emphysema, and pulmonary fibrosis and found that CF lung samples had higher levels of IL‐17A and that this correlated with high microbial colonization 36 . Although IL‐17A is secreted by different lymphocyte populations due to bacterial or nonbacterial stimuli, the overproduction of IL‐17A observed in CF appears to be aggravated by increased microbial load, which accelerates end‐stage disease.…”

“…These findings agree with a recent study that compared CF, lung emphysema, and pulmonary fibrosis and found that CF lung samples had higher levels of IL-17A and that this correlated with high microbial colonization. 36 Although IL-17A is secreted by different lymphocyte populations due to bacterial or nonbacterial stimuli, the overproduction of IL-17A observed in CF appears to be aggravated by increased microbial load, which accelerates end-stage disease. In contrast, IL-10 remained elevated in pwCF pre-and post-ETI, suggesting continued stimuli from myeloid-and lymphoid-derived immune cells in response to pathogens or other inflammatory stimuli.…”