Table 1.

USPs and pathogenesis of IBD.

USPs	Pathogenesis of IBD	Expression	Mechanism/major finding	Patients/Model	References
USP7	Imbalance of intestinal immunity	Deficiency	Decreased ability of resolving inflammation	Adoptive-transfer-induced colitis	[102]
USP8	Imbalance of intestinal immunity	Deficiency	Disturbed T cell homoeostasis, impaired T cell regulatory function, predominance of CD8+ γδ T cells	T cell-specific USP8-deficient colitis in mice	[103]
USP9X	Defect of intestinal barrier	Decrease	Decreased FBW7, tissue damage	DSS-induced colitis	[91]
USP9X	Defect of intestinal barrier	Inactive	Impaired intestinal regeneration	Colitis-associated intestinal cancer	[91]
Usp22	Defect of intestinal barrier	Deficiency	Moderate and severe epithelial damage; increases local and systemic inflammation	DSS-induced colitis	[90]
Usp22	Imbalance of intestinal immunity	Deficiency	Increases IL-6 levels; increases local immune cell infiltration and systemic inflammation in CD45-positive immune regulatory cells	DSS-induced colitis; inflammation-associated CRC murine model	[90]
USP25	Defect of intestinal barrier	Deficiency	Increased Paneth cells and IECs, epithelial damage	DSS-induced colitis	[61]
USP25	Imbalance of intestinal immunity	Deficiency	Higher expression of IRF-dependent genes and genes related to inflammatory cytokines and chemokines	DSS-induced colitis	[61]
USP25	Imbalance of intestinal immunity	Deficiency	increased phosphorylated p38 and p65, decreased TRAF3 and elevated IL-6 and TNF-α	Colitis infected by Citrobacter rodentium	[61]
CYLD	Defect of intestinal barrier	Deficiency	Histologic damage, greater leucocyte infiltration, histologic damage, and increased intestinal epithelial dysplasia	AOM and DSS-induced colitis-associated cancer model	[34]
CYLD	Defect of intestinal barrier	Deficiency	Enhanced bacterial dissemination, greater submucosal oedema and broader mucosal impairment and ulceration	Citrobacter rodentium induced colitis	[88]
CYLD	Imbalance of intestinal immunity	Deficiency	Higher concentration of IL-18	Colitis infected by Citrobacter rodentium	[88]
CYLD	Imbalance of intestinal immunity	High/low gene expression	Low/high production of IL-18	Patients with UC	[88]
CYLD	Defect of intestinal barrier	Inactive	Decreased intestinal epithelial cell death	Colitis in mice by FADD deficiency in IECs	[89]
CYLD	Imbalance of intestinal immunity	Deficiency	Increased cytokines including IL-10	Colitis with transferred T cell	[33]
sCYLD	Imbalance of intestinal immunity	Increase	Enhanced SMAD7 translocation, impaired suppressive function of Treg cells	sCYLD/SMAD7 mice	[98]
CYLD	Disturbance of gut microbiota	Decrease	Increased invasion and intracellular replication of AIEC bacteria.	Transfected T84 IECs	[77]
CYLD	Disturbance of gut microbiota	Increase	Decreased number of AIEC bacteria	Transfected T84 IECs	[77]
USP1	Genetic susceptibility	–	SNP (rs1748195) in USP1 gene is associated with CD risk	Patients with CD	[83]
USP3	Genetic susceptibility	–	Polymorphisms in USP3 genes are associated with both CD and UC	Patients with IBD	[77]
USP4,	Genetic susceptibility	–	Polymorphisms in USP4 genes are associated with both CD and UC	Patients with IBD	[74, 77, 82]
USP3, USP5, USP15, USP19, USP39	Genetic susceptibility	–	Polymorphisms in USP5, 15, 18, 39 genes are associated with UC	Patients with UC	[82]
USP25	Genetic susceptibility	–	Two SNPs, rs7278277 and rs2242830, are associated with CD and IBD, respectively	Patients with IBD	[79]
USP40	Genetic susceptibility	–	Polymorphisms in USP4 genes are associated with both CD and UC	Patients with IBD	[74, 77, 82]
USP44	Genetic susceptibility	–	USP44 methylation relevant to neoplasia associated IBD	Patients with neoplasia associated IBD	[81]
CYLD	Genetic susceptibility	–	The most important gene of ubiquitin proteasome system that associated with CD	Patients with CD	[76–78]