• TL1A binds to death receptor 3 (DR3) to provide stimulatory signals for downstream signaling pathways, thereby regulating the proliferation, activation, apoptosis of effector cells, and the production of cytokines and chemokines. Soluble decoy receptor 3 (DcR3) may neutralize the effects of sTL1A/DR3. In addition, DcR3 can inhibit apoptosis, reduce inflammation, and prevent tissue damage by neutralizing LIGHT and FasL. 
• IL-23 is a heterodimeric cytokine composed of p40 and p19 subunits, primarily produced by macrophages and dendritic cells. IL-23 binds to its receptor IL-23R, which regulates the release of downstream pro-inflammatory cytokines.
• The genome of the mouse Tl1a gene encoding the extracellular domain was replaced with its human TL1A counterpart in B-hTL1A/hIL23A/hIL12B mice. The genome of the mouse Il23a gene encoding the full-length protein was replaced with human IL23A counterpart in B-hTL1A/hIL23A/hIL12B mice. The genome of the mouse Il12b gene encoding the full-length protein was replaced with human IL12B counterpart in B-hTL1A/hIL23A/hIL12B mice. 
• Soluble human TL1A and human IL23 were exclusively detectable in homozygous B-hTL1A/hIL23A/hIL12B mice, but not in WT mice. Humanization of TL1A, IL23A and IL12B do not change the overall frequency or distribution of immune cell types in spleen, blood and lymph nodes. Humanization of TL1A, IL23A and IL12B do not change the blood cell composition and morphology, ALT and AST levels or health of liver. 
• This product is used for pharmacological and safety evaluation of autoimmune diseases such as Inflammatory bowel disease, psoriasis and arthritis.

Species specific analysis of TL1A, IL23A and IL12B gene expression in wild-type C57BL/6 mice and homozygous B-hTL1A/hIL23A/hIL12B mice by RT-PCR. Colon and lung were collected from wild-type C57BL/6 mice (+/+) and homozygous B-hTL1A/hIL23A/hIL12B mice (H/H). Mouse Tl1a, Il23a and Il12b mRNA were detectable only in wild-type C57BL/6 mice. Human TL1A/hIL23A/hIL12B mRNA were detectable only in homozygous B-hTL1A/hIL23A/hIL12B mice, but not in wild-type C57BL/6 mice. 

Soluble TL1A expression analysis in B-hTL1A/hIL23A/hIL12B mice by ELISA. Bone marrow derived dendritic cells were produced by culturing the bone marrow from wild-type C57BL/6 mice and homozygous B-hTL1A/hIL23A/hIL12B mice (female, 9-week-old, n=3), which were stimulated with LPS in vitro. After stimulation, the supernatants were collected and the levels of soluble TL1A was analyzed by ELISA. Soluble human TL1A was exclusively detectable in homozygous B-hTL1A/hIL23A/hIL12B mice, but not in wild-type C57BL/6 mice. Values are expressed as mean ± SEM. ND: not detectable. 

Strain specific IL23 expression analysis in wild-type C57BL/6 mice and homozygous humanized B-hTL1A/hIL23A/hIL12B mice by ELISA. Bone marrow derived dendritic cells were produced by culturing the bone marrow from wild-type C57BL/6 mice and homozygous B-hTL1A/hIL23A/hIL12B mice (female, 9-week-old, n=3), which were stimulated with LPS in vitro. After stimulation, the supernatants were collected and the levels of mouse and human IL23 were analyzed by ELISA. Mouse IL23 was only detectable in wild-type C57BL/6 mice. Human IL23 was exclusively detectable in homozygous B-hTL1A/hIL23A/hIL12B mice. Values are expressed as mean ± SEM. ND: not detectable. 

Frequency of leukocyte subpopulations in spleen by flow cytometry. Splenocytes were isolated from wild-type C57BL/6 mice and homozygous B-hTL1A/hIL23A/hIL12B mice (female, 7-week-old, n=3). A. Flow cytometry analysis of the splenocytes was performed to assess the frequency of leukocyte subpopulations. B. Frequencies of T cell subpopulations. Percentages of T cells, B cells, NK cells, DCs, monocytes, macrophages, neutrophils, CD4+ T cells, CD8+ T cells and Tregs in B-hTL1A/hIL23A/hIL12B mice were similar to those in C57BL/6 mice, demonstrating that humanization of TL1A, IL23A and IL12B do not change the frequency or distribution of these cell types in spleen. Values are expressed as mean ± SEM. 

Frequency of leukocyte subpopulations in blood by flow cytometry. Blood cells were isolated from wild-type C57BL/6 mice and homozygous B-hTL1A/hIL23A/hIL12B mice (female, 7-week-old, n=3). A. Flow cytometry analysis of the blood cells was performed to assess the frequency of leukocyte subpopulations. B. Frequencies of T cell subpopulations. Percentages of T cells, B cells, NK cells, DCs, monocytes, macrophages, neutrophils, CD4+ T cells, CD8+ T cells and Tregs in B-hTL1A/hIL23A/hIL12B mice were similar to those in C57BL/6 mice, demonstrating that humanization of TL1A, IL23A and IL12B do not change the frequency or distribution of these cell types in blood. Values are expressed as mean ± SEM. 

Frequency of leukocyte subpopulations in lymph node by flow cytometry. Leukocytes were isolated from wild-type C57BL/6 mice and homozygous B-hTL1A/hIL23A/hIL12B mice (female, 7-week-old, n=3). A. Flow cytometry analysis of the leukocytes was performed to assess the frequency of leukocyte subpopulations. B. Frequencies of T cell subpopulations. Percentages of T cells, B cells, NK cells, CD4+ T cells, CD8+ T cells and Tregs in B-hTL1A/hIL23A/hIL12B mice were similar to those in C57BL/6 mice, demonstrating that humanization of TL1A, IL23A and IL12B do not change the frequency or distribution of these cell types in lymph node. Values are expressed as mean ± SEM. 

B-hTL1A/hIL23A/hIl12B mice (male, 8-week-old, n=6) were given different concentrations of DSS in drinking water for 7 days. Control mice were given water only. On day 8, mice were sacrificed and monitored for colitis. (A) Schematic diagram of DSS induced IBD model. (B) Body weights and body weight changes. (C) Clinical score. (D) Changes in the length and weight of the colon. (E) Analysis of inflammatory cell infiltration and crypt loss/ulceration in the colon. (F) Representative images of H&E stained staining of colon sections (×20). The results showed that DSS induced IBD disease model was established in B-hTL1A/hIL23A/hIL12B mice, and higher concentrations of DSS lead to more severe inflammatory bowel disease phenotypes in B-hTL1A/hIL23A/hIL12B mice. Values are expressed as mean ± SEM. Significance was determined by two-way ANOVA test or One way ANOVA. ****p<0.0001, ***p<0.001 , **p<0.01 , *p<0.05.