Interleukin-22 and interleukin-22-producing NKp44+ natural killer cells in subclinical gut inflammation in ankylosing spondylitis

Objective The intestinal inflammation observed in patients with ankylosing spondylitis (AS) is characterized by an overexpression of interleukin‐23 (IL‐23). IL‐23 is known to regulate IL‐22 production through lamina propria NKp44+ natural killer (NK) cells, which are thought to be involved in protective mucosal mechanisms. This study was undertaken to evaluate the frequency of NKp44+ NK cells and the expression of IL‐22 in the ileum of AS patients. Methods Tissue NKp44+ NK cells, NKp46+ NK cells, and IL‐22–producing cells were analyzed by flow cytometry. Quantitative gene expression analysis of IL‐22, IL‐23, IL‐17, STAT‐3, and mucin 1 (MUC‐1) was performed by reverse transcriptase–polymerase chain reaction on ileal samples from 15 patients with AS, 15 patients with Crohn's disease (CD), and 15 healthy controls. NKp44, pSTAT‐3, and IL‐22 expression was analyzed by immunohistochemistry. Results The frequency of NKp44+ but not NKp46+ NK cells was increased in the inflamed ileum of AS patients compared to CD patients and controls. The frequency of NKp46+ NK cells was significantly increased only in CD patients. Among CD4+ lymphocytes and NKp44+ NK cell subsets, the latter were the major source of IL‐22 on lamina propria mononuclear cells from AS patients. Significant up‐regulation of IL‐22, IL‐23p19, MUC‐1, and STAT‐3 transcripts in the terminal ileum of patients with AS was observed. Immunohistochemical analysis confirmed the increased IL‐22 and pSTAT‐3 expression in inflamed mucosa from AS and CD patients. Conclusion Our findings indicate that overexpression of IL‐22, together with an increased number of IL‐22–producing NKp44+ NK cells, occurs in the gut of AS patients, where it appears to play a tissue‐protective role.