# CCL11 as a New Therapeutic Target for Colitis and Colon Cancer

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2020 · —

## Abstract

With more than 1.6 million Americans affected, inflammatory bowel disease (IBD) causes significant morbidity
and can progress to colon cancer. There are two main forms of IBD: ulcerative colitis (UC) and Crohn's
disease, and the associated abnormal immune response continues to be investigated with the goal of
discovering new therapeutics or avenues for intervention. We have previously shown that in a prospectively
collected cohort of adult UC patients, CCL11 (also called eotaxin-1), a chemoattractant for eosinophils, was the
only analyte increased in both serum and tissue at all levels of disease severity out of 42 cytokines and
chemokines assessed, compared to non-IBD control patients. We also observed a significant increase in
colonic tissue eosinophils in UC patients vs. controls, and eosinophil counts correlated with tissue CCL11
levels. It has been shown that Ccl11-deficient mice were protected from colitis in an acute dextran sulfate
sodium (DSS)-induced colitis model. However, acute colitis studies in mice lacking eosinophils have been
mixed, suggesting it is not clearly just decreased tissue eosinophil infiltration leading to improvement. We have
now determined that 1) Ccl11 mRNA is expressed in isolated colonic epithelial cells and isolated lamina
propria cells in response to the chronic DSS and the azoxymethane (AOM)-DSS colitis-associated
carcinogenesis (CAC) models; 2) epithelial cells and macrophages express receptors for CCL11; 3) treatment
with an anti-CCL11 antibody leads to protection in an injury and repair model of colitis; 4) Ccl11–/– mice exhibit
decreased tumor number, tumor burden, and colonic eosinophils in the AOM-DSS model; 5) bone marrow
transplant studies point to loss of both hematopoietic and epithelial-derived CCL11 as key mediators of the
protection seen in the AOM-DSS model; 6) CCL11 expression is increased in Apc mutant mouse tumors; and
7) the fecal microbiome is altered in Ccl11–/– mice compared to wild-type mice at baseline. In this proposal, we
will dissect the role of CCL11 in modulating epithelial injury and repair, and immune responses in models of
chronic colitis, CAC, and sporadic/genetically-mediated colon cancer. Our Hypothesis is: CCL11 is a key
mediator of colonic inflammation, epithelial dysfunction, and risk for carcinogenesis. The overarching
goal is to establish new insights into the potential benefits of blocking CCL11 signaling in both the treatment of
colitis and prevention of colon carcinogenesis. The Specific Aims are: 1. To determine the mechanism of
protection in colitis-associated cancer with loss of CCL11. Ccl11–/– mice exhibit protection in the AOM-
DSS model associated with altered tissue cytokine levels and decreased tissue eosinophils. However, acute
colitis studies in eosinophil-deficient mice suggest this may be an eosinophil independent effect. WT, Ccl11fl/fl,
Ccl11∆mye, Ccl11∆GIepi, and Ccl11–/– mice exposed to AOM-DSS will be used to test the hypothesis that
protective effects a...

## Key facts

- **NIH application ID:** 9940686
- **Project number:** 5I01BX004366-02
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Lori A Coburn
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9940686

## Citation

> US National Institutes of Health, RePORTER application 9940686, CCL11 as a New Therapeutic Target for Colitis and Colon Cancer (5I01BX004366-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9940686. Licensed CC0.

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