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2014 ; 20
(12
): 2412-32
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Emerging significance of NLRs in inflammatory bowel disease
#MMPMID25153506
Davis BK
; Philipson C
; Hontecillas R
; Eden K
; Bassaganya-Riera J
; Allen IC
Inflamm Bowel Dis
2014[Dec]; 20
(12
): 2412-32
PMID25153506
show ga
Pattern recognition receptors are essential mediators of host defense and
inflammation in the gastrointestinal system. Recent data have revealed that
toll-like receptors and nucleotide-binding domain and leucine-rich
repeat-containing proteins (NLRs) function to maintain homeostasis between the
host microbiome and mucosal immunity. The NLR proteins are a diverse class of
cytoplasmic pattern recognition receptors. In humans, only about half of the
identified NLRs have been adequately characterized. The majority of
well-characterized NLRs participate in the formation of a multiprotein complex,
termed the inflammasome, which is responsible for the maturation of
interleukin-1? and interleukin-18. However, recent observations have also
uncovered the presence of a novel subgroup of NLRs that function as positive or
negative regulators of inflammation through modulating critical signaling
pathways, including NF-?B. Dysregulation of specific NLRs from both
proinflammatory and inhibitory subgroups have been associated with the
development of inflammatory bowel disease (IBD) in genetically susceptible human
populations. Our own preliminary retrospective data mining efforts have
identified a diverse range of NLRs that are significantly altered at the
messenger RNA level in colons from patients with IBD. Likewise, studies using
genetically modified mouse strains have revealed that multiple NLR family members
have the potential to dramatically modulate the immune response during IBD.
Targeting NLR signaling represents a promising and novel therapeutic strategy.
However, significant effort is necessary to translate the current understanding
of NLR biology into effective therapies.