LILRA3 is increased in IBD patients and functions as an
anti-inflammatory modulator
Abstract
Growing evidence shows that a homozygous 6.7-kb deletion of the novel
anti-inflammatory molecule leukocyte immunoglobulin like receptor A3
(LILRA3) is associated with many autoimmune disorders. However, its
effects on pathogenesis of inflammatory bowel disease (IBD) have not
been clarified yet. LILRA3 is mainly expressed in monocytes, whereas its
effects on biological behaviors of monocytes have not been
systematically reported. To investigate the association between LILRA3
polymorphism and IBD susceptibility, LILRA3 polymorphism was assessed in
378 IBD patients and 509 healthy controls in our study, quantitative
real-time PCR (qRT-PCR), western blot and immunohistochemistry (IHC)
were employed to detect the LILRA3 expression in IBD patient blood and
intestinal samples. Despite no association of the polymorphism with IBD
development was found, LILRA3 expression was markedly increased in IBD
patients compared with healthy controls. Human U937 monocyte cell line
was employed to establish LILRA3-overexpressing cells and the effects of
LILRA3 on the biological behaviors of U937 cells were systematically
explored. We found that overexpression of LILRA3 in monocytes led to
significant decreases in secretion of interferon-γ (IFN-γ), tumor
necrosis factor-α (TNF-α) and interleukin 6 (IL-6). Additionally, LILRA3
abated monocyte migration by reducing the expression of several
chemokines and enhanced monocyte phagocytosis by increasing CD36
expression. Furthermore, LILRA3 promoted monocyte proliferation through
a combination of Akt and MEK/Erk signaling pathways. We report for the
first time that LILRA3 is related to IBD and functions as an
anti-inflammatory modulator in U937 cells.