# IgA antibody restrains colonic epithelial growth and tumour risk in mice via the DMBT1 protein

- Published: 2026-11-13 05:45 UTC
- Section: Life & Health › Biology & biochemistry
- Tags: immunoglobulin A, IgA deficiency, colorectal cancer in mice, DMBT1 protein, colonic epithelial proliferation, gut microbiota, mucosal homeostasis, CRISPR screening, colonocyte progenitors
- URL: https://realtech.media/news/rt-651da67b5021f45a5676a0f9_iga_antibody_restrains/

**In mouse models, IgA deficiency increased susceptibility to colorectal cancer; the antibody tempers epithelial cell cycling through the surface protein DMBT1, the authors report.**

![IgA antibody restrains colonic epithelial growth and tumour risk in mice via the DMBT1 protein](https://realtech.media/media/2026/11/130098be6f9bb211.jpg)
*Otávio Astor Vaz Costa, Wikimedia Commons, CC BY 4.0*

Researchers working with genetically and environmentally controlled mice report that immunoglobulin A (IgA), the most abundant antibody isotype produced by mammals, suppresses the proliferation of colonic epithelial cells and protects against colorectal tumours. The work was published in «Nature» [1]. Various models of IgA deficiency increased susceptibility to several models of endogenous colorectal cancer [1].

IgA is constantly secreted into the intestinal lumen and binds commensal microorganisms, regulating their colonization and function. Its implications for health have remained unclear. IgA deficiency is common in humans but difficult to study because of its complex aetiology and comorbidities, which is why the authors used controlled mouse models.

## Effect on the epithelium

Cellular and molecular analyses showed that in the absence of IgA, colonic epithelial cells induce antibacterial factors and accelerate cell cycling in response to the microbiota [1]. Oral IgA was sufficient to reduce steady-state proliferation and protect mice from tumours [1].

This protective effect depended on the structure of the antibody rather than on its binding specificity, according to the authors [1]. In a reductionist culture system, IgA directly suppressed epithelial growth [1].

## The role of DMBT1

Co-immunoprecipitation mass spectrometry and targeted CRISPR screening identified DMBT1 as an IgA-binding protein on the epithelial surface that is required for IgA-mediated suppression of proliferation [1]. Together, IgA and DMBT1 tune the normal cycling of absorptive colonocyte progenitors [1].

In IgA-knockout mice, deleting the transmembrane and cytoplasmic signalling portions of DMBT1 was sufficient to reverse both the increased epithelial cell proliferation and the increased tumour susceptibility [1]. The authors conclude that IgA has a homeostatic function: it tempers physiological epithelial responses to the microbiota and so helps maintain mucosal health [1].

The results were obtained in mice and in cell culture; the material reports no data from human patients.

## Sources

1. [Nature](https://doi.org/10.1038/s41586-026-11264-2)

---

Source: RealTech, realtech.media — https://realtech.media/news/rt-651da67b5021f45a5676a0f9_iga_antibody_restrains/