Customized Anti-CD40-Induced Colitis Models

The CD40-CD40 ligand (CD154) costimulatory system has been implicated in the pathogenesis of inflammatory bowel disease (IBD) due to its role in cell-mediated immunity and to overexpression of CD40 and CD40L in intestinal tissue from patients with Crohn's disease (CD) and ulcerative colitis (UC). Stimulation of CD40 by an agonist anti-CD40 antibody in T and B cell-deficient mice results in an activation of an innate immune response in the gut that includes upregulation of IL-23 mRNA and IL-12 mRNA by myeloid cells, elevated proinflammatory serum cytokines, and inflammation of the colon. This model is well suited to study the innate immune response in IBD. Inhibition of TNF, IFNγ, or IL-12/IL-23 p40 reduces or blocks disease development.

Fig. 1. Inducing colitis symptoms in mice by injecting antibodies against the CD40 antigen. Fig. 1. Induction and analysis of the anti-CD40 colitis mouse model. (Joyce-Shaikh et al., 2019)

Our Anti-CD40-Induced Colitis Models

Ace Therapeutics establish a stable IBD model in Rag2-/- or CB-17 SCID mice using the agonistic CD40 monoclonal antibody, which can be used for preclinical IBD studies and pharmacodynamic evaluation.

Our experienced team of specialists has extensive expertise in a wide range of study designs in pharmacology, toxicology, and IBD modeling. We can assist you from model construction to pharmacodynamic evaluation, providing reliable and reproducible results.

Description	Our murine anti-CD40 colitis model of IBD is a unique model of colitis driven by IL-23-producing gut resident CX3CR1⁺ macrophages and IL-22-producing group 3 innate lymphoid cells (ILC3).
Modeling Method	Colitis is induced via administration of an agonistic CD40 monoclonal antibody to T and B cell-deficient C57BL/6 RAG2-/- or CB-17 SCID mice. Naïve RAG2-/- or CB-17 SCID mice inject with PBS in lieu of anti-CD40 antibodies are used as a negative control for colitis.
Features	This model is short, with significant elevation in serum cytokines on Day 1 after anti-CD40 injection. Anti-CD40-treated Rag2-/- or CB-17 SCID mice lose up to 20% of their initial weight within three days post injection By Day 5, colon weight to length ratio is significantly increased over naïve mice, and significant colon pathology is observable. Characterized by massive infiltration of innate immune cells, loss of goblet cells and development of mitotic figures–is observed in the proximal colon at day 7 post disease induction.
Applications	For studying the role of innate immune cells during acute intestinal inflammation. For drug development for experiments requiring a macrophage-mediated mechanism of action, but not requiring lymphocytes.

Preclinical Evaluation in Anti-CD40-Induced Colitis Models

We offer a combination of reliable and reproducible methods for analyzing anti-CD40 induced colitis in mice. Our scientists will review your preliminary results with you and can recommend the best analyses to maximize the return on your research.

Percentage change in body weight
Colon weight and length measurements
Histopathologic analysis by H&E staining
Fecal LCN2, calreticulin and MPO analysis
Measurement of cytokine concentrations in colonic culture supernatants or sera
Flow cytometric analysis of lamina propria and/or lymphoid organs
Proximal colon gene expression profiling

Ace Therapeutics provides reliable animal models of anti-CD40-induced colitis to pharmaceutical, biotech, and academic clients around the world. We aim to accelerate your preclinical IBD research. For questions or to request a quote, please contact us.

Reference

Joyce-Shaikh, B., et al. (2019). Induction and analysis of anti-CD40-induced colitis in mice. Bio-protocol, 9(3), e3153-e3153.

! For research use only, not intended for any clinical use.