Table 1.

Genetic factors affect IBD by regulating the activation of inflammasomes.

Gene	Function to Inflammasome	Mechanism	Deficiency or Variant	Variant Impact to Disease	Disease or Model	Reference
IRGM	Inhibit NLRP3 inflammasome assambly	Interact with NLRP3 and Promote NLRP3 autophagic degradation	Deficiency	Exacerbate colitis	DSS-colitis in mouse	[49]
RIPK1	Inhibit NLRP3 inflammasome activation upon LPS stimulation	Not clear	Deficiency	Primary immunodeficiency and/or colitis	Human colitis	[51]
BTK	Inhibit NLRP3 inflammasome activation	Inhibit PP2A mediated NLRP3 dephosphorylation	Deficiency	Exacerbate colitis	DSS-colitis, TNBS-colitis in mouse	[53]
PTPN2	Inhibit NLRP3 inflammasome activation	Inhibit JNK and ASC phosphorylation	Deficiency in myeloid cell	Exacerbate colitis	DSS-colitis in mouse	[54]
Jmjd3	Enhance NLRP3 inflammasome activation	Prevent H3K27me3 mediated inhibition of Nrf2	Inhibition or Knock-down	Ameliorate colitis	DSS-colitis	[55]
miR-223	Inhibit NLRP3 inflammasome activation	Bind to NLRP3 3’ untranslated region to inhibit inflammasome assembly	Deficiency	Exacerbate colitis	DSS-colitis in mouse	[56]
NLRP3 mutation	Enhance NLRP3 inflammasome activation	Enhance deubiquitination of NLRP3 via binding with BRCC3 and JOSD2	R779C	Exacerbate colitis	DSS-colitis in mouse	[61]
COMMD10	Inhibit NLRP3 inflammasome activation	Inhibit transcription of inflammasome components	Deficiency in monocytes	Exacerbate colitis	DSS-colitis in mouse	[62]
CARD8	Inhibit NLRP3 inflammasome assembly	Interact with NLRP3 and inhibit NLRP3 oligomerization	V44I	Exacerbate colitis	Crohn’s disease	[63]
IL-10R	Inhibit NLRP3 inflammasome activation	Inhibit expression of NLRP3 and IL-1β	Deficiency	Spontaneous colitis in mouse and infant-onset IBD in human	Mouse spontaneous colitis and human IBD	[64]
NADPH oxidase	Inhibit NLRP3 inflammasome activation	Induce autophagy	Deficiency	Exacerbate colitis	TNBS-colitis in mouse	[65]
CD1d1	Reduce transcription of NLRP3 inflammasome components	Reduce peroxiredoxin 1/ATK/STAT1 mediated NF-kB signaling	Deficiency in macrophage	Ameliorate colitis	DSS-colitis in mouse	[44]
PTPN22	Enhance NLRP3 inflammasome activation	Induce NLRP3 dephosphorylation at Tyr861	Deficiency	Exacerbate colitis	DSS-colitis in mouse	[45]
			V619W	Ameliorate colitis	DSS-colitis in mouse	[45]

Abbreviations: IRGM: Immunity-related GTPase family M; RIPK1: Receptor interacting protein kinase 1; BTK: Bruton’s tyrosine kinase; XLA: X-linked agammaglobulinemia; PTPN2, 22: protein tyrosine phosphatase non-receptor type 2, 22; Jmjd3: Jumonji domain-containing 3; VEOIBD: Very-Early-Onset inflammatory bowel disease; COMMD10: COMM domain containing 10; CARD8: caspase recruitment domain family member 8; CGD: chronic granulomatous disease; PP2A: serine/threonine protein phosphatase 2A; DSS: Dextran Sodium Sulfate; TNBS: 2,4,6-trinitrobenzene sulfonic acid; PPARγ: peroxisome proliferator-activated receptor γ; SO₂: sulfur dioxide; and CysA: cyclosporin A.