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

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.