| T-bet and RAG2 |
T-bet−/− × RAG2−/− mice (or TRUC mice for T-bet−/− × RAG−/− ulcerative colitis) |
Colitogenic microbiota: vertically and horizontally transmissible, the presence of Klebsiella pneumoniae and Proteus mirabilis correlates with colitis |
Spontaneous colitis, anorectal prolapse, rectal inflammation |
Colonic thickening, surface ulceration, crypt distortion and hyperplasia, dense mixed inflammatory cell infiltrate in the LP |
Continuous inflammation of the rectum and left colon, marked inflammation, increased colonic permeability |
TNFα (colonic DCs)/TNFR1/p55, commensal microbiota (anaerobic bacteria) |
Garrett et al.121, 122
|
| IL-10 |
IL-10−/− mice |
ND |
Spontaneous chronic enterocolitis of the entire intestinal tract, weight loss, splenomegaly, anemia, lethality for 30% of the animals |
Mucosal inflammation, epithelial hyperplasia, abnormal crypt and villus structures, crypt abscesses, ulcers, mucin depletion, erosions of the mucosa, thickening of bowel wall |
Aberrant immune cell activation and increase of immune cells, Th1 polarization, deposits of fibrinoid material and IgA, aberrant expression of MHC class II molecules in intestinal epithelia, reduction of Treg in the large intestinal LP, increase of B1 lymphocytes (CD19+CD5+), enhanced levels of serum IgG and IgA |
Enteric microbial flora, MyD88-dependent, IL-23 |
Kühn et al.,123 Rakoff-Nahoum et al.124 and Gomes-Santos et al.125
|
| IL-2 |
IL-2−/− mice or IL-2−/−Myd88−/−
|
ND |
Spontaneous colitis, rectal prolapse, wasting, mortality, thickening of the bowel wall, shortening colonic length, unformed or absent stool |
Multifocal, transmural leukocytic infiltrate, severe epithelial hyperplasia, destruction of crypt architecture |
Aberrant CD4+ T-cell activation, increase of DCs in MLN, Th1 polarization, |
Commensal microflora-dependent, MyD88-independent, IL-12- or IL-23-independent factors |
Rakoff-Nahoum et al.124
|
| IL-15 |
IL-15−/− mice+2–3% DSS |
ND |
Attenuated induced chronic colitis, increased survival rate, less weight loss, bleeding and diarrhea than WT mice, inhibition of colon shortening |
Reduced numbers of infiltrating cells, degree of mucosal injury and edema |
Low levels of IFNγ, TNFα and IL-12p40 in the large intestine LPs |
CD8+ T cells, NK cells, DCs? |
Yoshihara et al.126
|
| IL-22 |
IL-22−/− mice+2 or 3% DSS |
High diversity microbiota, 7 reduced genera (Lactobacillus, Bacteroides, Ruminococcus, Turicibacter, Anaerobacter, Parabacteroides and Hespellia) and 7 increased genera (Coprococcus, Allobaculum, Barnesiella, Alistipes, Xylanibacter, Butyricimonas and Helicobacter), transmissible colitic microbiota |
Induced colitis, more weight loss and higher rate of mortality than WT mice |
|
Reduced expression of RegIIIβ and RegIIIγ
|
NK cells, dependent and independent role of intestinal microbiota |
Zenewicz et al.127, 128
|
| IDO (indoleamine 2,3-dioxygenase) |
Transplantation of Ido1−/− BM cells in Ido1+/+ mice+TNBS (A) or Ido1−/− mice+TNBS or 1-mT (IDO inhibitor) in Ido1+/+ mice+TNBS (B) |
ND |
(A) More severe colitis than with Ido1+/+ BM cells transplanted; (B) more severe colitis in Ido1−/− mice+TNBS than WT+TNBS, phenotype of WT mice treated with 1-mT+TNBS similar to Ido1−/− mice+TNBS and decrease of survival and colonic dilation with stool retention |
Severe colonic transmural inflammation, changes in mucosal architecture (extensive ulceration and coagulation necrosis) in Ido1−/− mice+TNBS and 1-mT+TNBS-treated WT mice |
(A) Higher expression of Ifng and Tnf and decreased Foxp3/CD4 ratio in the colons than with Ido1+/+ BM cells transplanted; (B) Increased expression of IL-12, IFNγ and IL-2 in TNBS+1-mT-treated mice |
Suppression of inflammation mainly by IDO-expressing colonic inflammatory cells and contribution of IDO-expressing colonic epithelium, IFNγ (STAT1) |
Takamatsu et al.129 and Gurtner et al.130
|
| WASP (Wiskott–Aldrich syndrome protein) |
WASP KO mice (WKO mice) |
ND |
Frequent signs of colitis (wasting, rectal prolapse, diarrhea), thickening and shortening of the colon, extensive enlargement of mesenteric LNs and spleen |
Crypt elongation, epithelial hyperplasia, extensive LP infiltration of inflammatory cells, occasional crypt abscesses, depletion of goblet cells |
LP infiltration by CD4+ T cells, CD8+ T cells, F4/80+ macrophages, neutrophils and CD11c+ dendritic cells, increase in activated CD4+ T cells in mesenteric and subcutaneous LNs and spleen, increase of IL-4, IL-13 and IFNγ in colonic LP cells |
CD4+ T cells, Treg, IL-10, tolerogenic DCs |
Nguyen et al.131, 132
|
| Runx3 |
Runx3 KO mice |
ND |
Spontaneous chronic colitis, cecal wall thickened, rigid and opaque, colon with tubular thickening, enlargement of the mesenteric LNs |
Multifocal and coalescing mixed mucosal and submucosal infiltration of plasma cells, lymphocytes, histiocytes and eosinophils, mucosal hyperplasia, crypt loss, increased mitotic figures, late-onset progressive proliferative gastritis |
Increase of T lymphocytes, macrophages and DCs in the mucosa, of lymphocytic clusters with B cells in the large intestine, IgA production, IFNγ, TNFα, IL-12, Tim-3, IL-4, T-bet and GATA-3 expression in the colon |
Leukocytic cell-autonomous function of Runx3 |
Brenner et al.133
|
| AhR (aryl hydrocarbon receptor) |
AhR KO mice+3.5% DSS |
ND |
Severe induced colitis, severe decrease in body weight, colon shortening |
More severe histological scores and severe inflammation for the colon tissue |
Increased mRNA expression level of TNFα, IL-6, IL-1β and IL-8 |
|
Furumatsu et al.134
|
| PD-1 (program death-1) |
Adoptive transfer of naive CD4+CD25− T cells from PD-1−/− mice to Rag1−/− mice |
ND |
T-cell transfer-induced colitis, body weight loss |
Severe lymphocyte infiltration, crypt dropout, epithelial regeneration, overall crypt architectural alteration in the colons |
Defect in de novo iTreg development, increase of Th17 cells in draining LNs |
Akt-dependent mechanism of iTreg development |
Qiao et al.135
|
