Group 3 innate
lymphoid cells (ILC3), which express
IL-22 and
IL-17A, has been introduced as one of pathologic
cells in
axial spondyloarthritis (
axSpA). Dyslipidaemia should be managed in
axSpA patients to reduce
cardiovascular disease, and dyslipidaemia promotes
inflammation. This study aimed to reveal the
role of circulating ILC3 in
axSpA and the impact of dyslipidaemia on
axSpA pathogenesis.
AxSpA patients with or without dyslipidaemia and healthy control were recruited. Peripheral
blood samples were collected, and
flow cytometry analysis of circulating ILC3 and CD4+
T cells was performed. The correlation between
Ankylosing Spondylitis Disease Activity Score (ASDAS)-
C-reactive protein (CRP) and circulating immune
cells was evaluated. The effect of oxidized
low-density lipoprotein cholesterol (oxLDL-C) on immune
cell differentiation was confirmed.
AxSpA human monocytes were cultured with with oxLDL-C,
IL-22, or oxLDL-C plus
IL-22 to evaluate
osteoclastogenesis using
tartrate-resistant acid phosphatase (TRAP)
staining and realtime quantitative
PCR of
osteoclast-related
gene expression. Total of 34
axSpA patients (13 with dyslipidaemia and 21 without) were included in the
analysis. Circulating
IL-22+ ILC3 and Th17 were significantly elevated in
axSpA patients with dyslipidaemia (p=0.001 and p=0.034, respectively), and circulating
IL-22+ ILC3 significantly correlated with ASDAS-CRP (Rho=0.4198 and p=0.0367). Stimulation with oxLDL-C significantly increased
IL-22+ ILC3, NKp44 − ILC3, and
Th17 cells, and these were reversed by CD36 blocking agent.
IL-22 and oxLDL-C increased TRAP +
cells and
osteoclast-related
gene expression. This study suggested potential
role of circulating
IL-22+ ILC3 as
biomarker in
axSpA. Furthermore, dyslipidaemia augmented
IL-22+ ILC3 differentiation, and oxLDL-C and
IL-22 markedly increased
osteoclastogenesis of
axSpA.