Expansion of Interleukin‐22– and Granulocyte–Macrophage Colony‐Stimulating Factor–Expressing, but Not Interleukin‐17A–Expressing, Group 3 Innate Lymphoid Cells in the Inflamed Joints of Patients With Spondyloarthritis

摘要

Objective Clinical trials of the anti–interleukin‐17A (anti– IL ‐17A) antibody secukinumab have demonstrated a crucial role of the cytokine IL ‐17A in the pathogenesis of spondyloarthritis (SpA); however, its cellular source in this condition remains a matter of controversy. Group 3 innate lymphoid cells ( ILC 3s) have been recently identified as potent producers of proinflammatory cytokines, including IL ‐17A and IL ‐22, in a number of different tissues. This study was undertaken to characterize the presence and composition of ILC s, and investigate whether these cells are an important source of IL ‐17A, in the synovial tissue ( ST ) of patients with SpA. Methods Matched ST , synovial fluid, and peripheral blood ( PB ) samples were obtained from SpA patients with actively inflamed knee joints. ILC subsets were characterized by flow cytometry. Gene expression analysis at the single‐cell level was performed directly ex vivo and after in vitro activation. An IL ‐17A enzyme‐linked immunospot assay was used to detect IL ‐17A–secreting cells. Results ILC s, and particularly NK p44+ ILC 3s, were expanded in inflamed arthritic joints. Single‐cell expression analysis demonstrated that ST ILC s were clearly distinguishable from ST T cells and from their PB counterparts. Expression of the Th17 signature transcripts RORC , AHR , and IL 23R was detected in a large proportion of ST ILC 3s. These cells were capable of inducing expression of IL 22 and CSF 2 , but not IL 17A , in response to in vitro restimulation. Conclusion Our findings demonstrate that absolute and relative numbers of ILC 3s are enriched in the synovial joints of patients with SpA. However, these cells are not a significant source of IL ‐17A in this disease.