Table 1 USPs and pathogenesis of IBD.

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

[76,77,78]