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.


CONCLUSIONS
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.
Università di Palermo, Palermo, Italy.
Francesco
F
Ciccia
Antonina
A
Accardo-Palumbo
Riccardo
R
Alessandro
Aroldo
A
Rizzo
Simona
S
Principe
Sergio
S
Peralta
Francesca
F
Raiata
Annarita
A
Giardina
Giacomo
G
De Leo
Giovanni
G
Triolo
D000328:Adult; D005260:Female; D006801:Humans; D007082:Ileum / Q000276:immunology* / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism; D055629:Natural Cytotoxicity Triggering Receptor 2 / Q000032:analysis*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013167:Spondylitis, Ankylosing / Q000276:immunology* / Q000378:metabolism; D000097043:Interleukin-22
D053759:Interleukin-23; D007378:Interleukins; D018396:Mucin-1; D055629:Natural Cytotoxicity Triggering Receptor 2; D050796:STAT3 Transcription Factor; D000097043:Interleukin-22; C112837:NCR2 protein, human