Table 4.

Regulation of immune-related structural cell functions by NLRX1.

IV. Regulation of Immune-Related Structural Cell Functions by NLRX1
Epithelial Cells and Fibroblasts
Cell Type	Model	Observed Effects	Mechanism	Ref.
NLRX1 silenced human airway epithelial cells	rhinovirus infection, poly (I:C) treatment	Silencing of NLRX1 abrogates virus induced epithelial barrier disruption and decreased ROS production	NLRX1 promotes mtROS production	[39]
NLRX1 silenced human HEK293T, HeLa	Sendai virus infection	Silencing of NLRX1 promotes type I IFN production and decreases viral replication	NLRX1 interferes with MAVS signaling and inhibits IRF3 dimer formation	[14]
NLRX1 silenced human HEK293T	Sendai virus infection	Silencing of NLRX1 has no effect on type I IFN response	-	[88]
NLRX1−/− mouse airway epithelial cells	mouse models of invasive pulmonary aspergillosis	NLRX1 deficiency enhances pulmonary inflammation and increases chemokine and cytokine production	NLRX1 impairs P38 phosphorylation	[73]
NLRX1−/− human BEAS-2B airway epithelial cells	Aspergillus fumigatus infection	NLRX1 deficiency enhances chemokine (CXCL8, CXCL1) and cytokine (IL-6) production	NLRX1 impairs P38 phosphorylation	[73]
human HEK293T	Overexpressed NLRX1, Shigella infection, TNFα treatment	Overexpression of NLRX1 facilitates NF-κB and JNK pathways	NLRX1 promotes ROS production	[43]
NLRX1 silenced human gingival epithelial cells	Fusobacterium nucleatum infection	Silencing of NLRX1 attenuates the NLRP3 inflammasome activity	NLRX1 promotes mtROS production	[89]
NLRX1 silenced human gingival epithelial cells	Fusobacterium nucleatum infection	Silencing of NLRX1 increases NF-κB activity and enhances IL-8 production	NLRX1 interferes with NF-κB pathway	[89]
NLRX1−/− mouse intestinal epithelial cells	DSS-induced colitis	NLRX1 deficiency increases proliferation, glutamine metabolism and pro-inflammatory cytokine production	NLRX1 interacts with SIRT1 and regulates glutamine metabolism	[56]
NLRX1−/− mouse MEFs	poly (I:C) stimulation	NLRX1 deficiency has no effect on MAVS-dependent IFNβ and IL-6 production	-	[62]
NLRX1−/− mouse MEFs	Sendai virus, EMCV and VSV infections	NLRX1 deficiency has no effect on MAVS-dependent IL-6, CXCL10, KC and IFNβ expression	-	[63]
NLRX1−/− mouse MEFs	EMCV infection	NLRX1 deficiency has no effect on EMCV induced IFN-β production mediated by MDA5 activation	-	[19]
NLRX1−/− mouse MEFs	Simian Virus, Sendai Virus, VSV and Influenza A virus infections	NLRX1 deficiency increases IFNβ and IL-6 production mediated by RIG-I activation	NLRX1 interferes with the RIG-I dependent MAVS signaling pathway	[19]
NLRX1−/− mouse MEFs	LPS treatment	NLRX1 deficiency enhances p65 phosphorylation and decreases IκBα level	NLRX1 binds to TRAF6 and interferes with NF-κB signaling	[19]
mouse MEFs	EYA4 overexpression, Escherichia coli infection, mammalian DNA or poly (I:C) treatments	Overexpression of EYA4 enhances IFNβ expression	EYA4 binds to NLRX1 and enhances IRF3 signaling	[68]
NLRX1−/− mouse MEFs	VSV infection	NLRX1 deficiency increases IL-6, TNF-α and type I IFN production	NLRX1 binds to TUFM/ATG5-ATG12 complex	[32]
NLRX1−/− mouse MEFs	VSV infection	NLRX1 deficiency decreases LC3B-II level which leads to defective autophagy	NLRX1 binds to TUFM/ATG5-ATG12 complex	[32]
NLRX1 silenced human HeLa cells, NLRX1−/− mouse MEFs	Chlamydia trachomatis infection	NLRX1 deficiency decreases the survival of the pathogen and the production of ROS	NLRX1 promotes ROS production and caspase-1 activation	[40]