Table 2.
Developed humanized mouse models to study IBD pathogenesis.
| Genetic Background of Mice | Induction of Colitis | Human Cells Transplanted | Remarks | References |
|---|---|---|---|---|
| NOD-SCID IL2Rγ−/− (NSG) | Allergen (Birch, grass, Hazelnut) | PBMCs from allergic and non-allergic subjects | The amplified extent of colitis was seen in allergic donors isolated PBMCs engrafted micecompared to healthy donors. | [206] |
| NSG | Oxazolone | PBMCs from healthy, UC and AD subjects | The described model showed the potential to study the efficacy of therapeutics targeting human lymphocytes in a model closely mimicking human ulcerative colitis. | [207] |
| NSG | TNBS | HLA-matched human CD4+ T cells | Adoptive transfer of human CD4+ T cells in humanized animals with TNBS induced small bowel enteropathy and promoted colonic inflammation. | [208] |
| HLA-matched CD34+ human HSCs from healthy and IPEX subjects | The study established the use of human HSCs to transfer disease phenotype in humanized mice to study human immune effectors and pathogenesis of IBD. | [209] | ||
| NSG | TNBS | HLA-matched human CD4+ T cells isolated from a healthy donor | The study developed an experimental humanized murine model to investigate human CD4+ T responses in vivo and identify the ITE (a non-toxic AHR agonist) as a potential therapy to achieving the immune tolerance in the intestine. | [210] |
| NSG | TNBS | PBMCs isolated from healthy donors | Low-dose IL-2 helped in expanding Trges for using as a therapeutic strategy against colitis in humanized mice. | [180] |
| NSG | PBMCs from UC donors were reconstituted in NSG mice and treated with oxelumab | NSG-UC mice treated with oxelumab significantly reduced clinical, colon and histological scores and reduced serum levels of IL-6. | [211] | |
| NSG | TNBS | Antisense+ CD4 cells isolated from a healthy donor | Silencing the endogenous antisense long non-coding RNA restores CD39 levels with enhancing Treg-suppressive function. | [212] |
| NSG | TNBS | CD34+ human HSCs | Low-dose (LD) IL-2 reduced the severity of TNBS induced in HSC CD34+ reconstituted NSG mice and paved the way for developing future therapeutic strategy based on LD IL-2 | [185] |
Abbreviations: NOD-SCID IL2Rγ−/−, non-obese diabetic mice with severe combined immunodeficiency and null mutation in the interleukin 2 (IL-2) receptor gamma chain; PBMCs, peripheral blood mononuclear cells; UC, ulcerative colitis, AD, atopic dermatitis; TNBS, tri-nitro-benzene-sulfonic acid; HSCs, hematopoietic stem cells; IPEX, immuno-dysregulation polyendocrinopathy enteropathy X-linked syndrome; ITE,2-(1′H-indole-3′-carbonyl) thiazole-4-carboxylic acid methyl ester; AHR, aryl hydrocarbon receptor.